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Pancreatic Neoplasms: HELP
Articles by Sapna Syngal
Based on 21 articles published since 2010
(Why 21 articles?)
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Between 2010 and 2020, Sapna Syngal wrote the following 21 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Editorial Intercepting Pancreatic Cancer: Our Dream Team's Resolve to Stop Pancreatic Cancer. 2018

Goggins, Michael G / Lippman, Scott M / Constantinou, Pamela E / Jacks, Tyler / Petersen, Gloria M / Syngal, Sapna / Maitra, Anirban. ·Division of Hematology/Oncology, Department of Medicine, Moores Center for Personalized Cancer Therapy, University of California, San Diego, La Jolla, CA. · Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN. ·Pancreas · Pubmed #30325853.

ABSTRACT: -- No abstract --

2 Editorial Germline Genetic Testing for Pancreatic Ductal Adenocarcinoma at Time of Diagnosis. 2018

Syngal, Sapna / Furniss, C Sloane. ·Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts. · Harvard Medical School, Boston, Massachusetts. · Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts. ·JAMA · Pubmed #29922810.

ABSTRACT: -- No abstract --

3 Review Hereditary pancreatic cancer. 2010

Grover, Shilpa / Syngal, Sapna. ·Department of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, USA. ·Gastroenterology · Pubmed #20727885.

ABSTRACT: -- No abstract --

4 Clinical Trial Mutations in the pancreatic secretory enzymes 2018

Tamura, Koji / Yu, Jun / Hata, Tatsuo / Suenaga, Masaya / Shindo, Koji / Abe, Toshiya / MacGregor-Das, Anne / Borges, Michael / Wolfgang, Christopher L / Weiss, Matthew J / He, Jin / Canto, Marcia Irene / Petersen, Gloria M / Gallinger, Steven / Syngal, Sapna / Brand, Randall E / Rustgi, Anil / Olson, Sara H / Stoffel, Elena / Cote, Michele L / Zogopoulos, George / Potash, James B / Goes, Fernando S / McCombie, Richard W / Zandi, Peter P / Pirooznia, Mehdi / Kramer, Melissa / Parla, Jennifer / Eshleman, James R / Roberts, Nicholas J / Hruban, Ralph H / Klein, Alison Patricia / Goggins, Michael. ·Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Health Sciences Research, Mayo Clinic, Rochester, MN 55905. · Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5. · Population Sciences Division, Dana-Farber Cancer Institute, Boston, MA 02215. · Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213. · Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Pancreatic Cancer Translational Center of Excellence, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10017. · Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109. · Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201. · The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada H3H 2R9. · The Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada H3A 1A3. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724. · InGenious Targeting Laboratory, Ronkonkoma, NY 11779. · Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; mgoggins@jhmi.edu. ·Proc Natl Acad Sci U S A · Pubmed #29669919.

ABSTRACT: To evaluate whether germline variants in genes encoding pancreatic secretory enzymes contribute to pancreatic cancer susceptibility, we sequenced the coding regions of

5 Article Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. 2020

Goggins, Michael / Overbeek, Kasper Alexander / Brand, Randall / Syngal, Sapna / Del Chiaro, Marco / Bartsch, Detlef K / Bassi, Claudio / Carrato, Alfredo / Farrell, James / Fishman, Elliot K / Fockens, Paul / Gress, Thomas M / van Hooft, Jeanin E / Hruban, R H / Kastrinos, Fay / Klein, Allison / Lennon, Anne Marie / Lucas, Aimee / Park, Walter / Rustgi, Anil / Simeone, Diane / Stoffel, Elena / Vasen, Hans F A / Cahen, Djuna L / Canto, Marcia Irene / Bruno, Marco / Anonymous1461018. ·Pathology, Medicine Oncology, Johns Hopkins University, Baltimore, Maryland, USA mgoggins@jhmi.edu. · Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. · GI Cancer Genetics and Prevention Program, Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA. · Department of Surgery, Division of Surgical Oncology, Denver, Colorado, USA. · Division of Visceral, Thoracic and Vascular Surgery, University of Marburg, Marburg, Germany. · Department of Surgey, University of Verona, Verona, Italy. · Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain. · Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. · The Russell H Morgan Department of Radiology and Radiological Science, Baltimore, Maryland, USA. · Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology & Metabolism, Amsterdam, The Netherlands. · Gastroenterology, Endocrinology, Metabolism and Infectiology, University of Marburg, Marburg, Germany. · Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands. · Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA. · Division of Digestive and Liver Diseases, Columbia University Medical Center, New York City, New York, USA. · Division of Digestive and Liver Diseases, Columbia University, New York City, New York, USA. · Oncology, Johns Hopkins University, Baltimore, Maryland, USA. · Medicine, Johns Hopkins University, Baltimore, Maryland, USA. · Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA. · New York University Medical Center, New York City, New York, USA. · University of Michigan, Ann Arbor, Michigan, USA. · Gastroenterology and Hepatology, Leiden University, Leiden, The Netherlands. ·Gut · Pubmed #31672839.

ABSTRACT: BACKGROUND AND AIM: The International Cancer of the Pancreas Screening Consortium met in 2018 to update its consensus recommendations for the management of individuals with increased risk of pancreatic cancer based on family history or germline mutation status (high-risk individuals). METHODS: A modified Delphi approach was employed to reach consensus among a multidisciplinary group of experts who voted on consensus statements. Consensus was considered reached if ≥75% agreed or disagreed. RESULTS: Consensus was reached on 55 statements. The main goals of surveillance (to identify high-grade dysplastic precursor lesions and T1N0M0 pancreatic cancer) remained unchanged. Experts agreed that for those with familial risk, surveillance should start no earlier than age 50 or 10 years earlier than the youngest relative with pancreatic cancer, but were split on whether to start at age 50 or 55. Germline CONCLUSIONS: Pancreatic surveillance is recommended for selected high-risk individuals to detect early pancreatic cancer and its high-grade precursors, but should be performed in a research setting by multidisciplinary teams in centres with appropriate expertise. Until more evidence supporting these recommendations is available, the benefits, risks and costs of surveillance of pancreatic surveillance need additional evaluation.

6 Article Health behaviours and beliefs in individuals with familial pancreatic cancer. 2019

Underhill-Blazey, Meghan / Blonquist, Traci / Lawrence, Janette / Hong, Fangxin / Yurgelun, Matthew B / Syngal, Sapna. ·Dana-Farber Cancer Institute, 450 Brookline Avenue, LW 522, Boston, MA, 02215, USA. meghanl_underhill@dfci.harvard.edu. · Dana-Farber Cancer Institute, 450 Brookline Avenue, LW 522, Boston, MA, 02215, USA. · Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. · Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02215, USA. ·Fam Cancer · Pubmed #31522335.

ABSTRACT: Individuals at high risk for pancreatic cancer are recommended surveillance and healthy lifestyle behaviours and patient experience with recommendations are understudied. To describe engagement and experience with surveillance, tobacco and alcohol use, health beliefs and motivation (Champion Health Belief Measure) and the relationship with personal, psychosocial (Impact of Event Scale), and familial characteristics. Interest in integrative therapies (complementary therapies) are described. A multi-site cross-sectional survey including individuals at high risk for pancreatic cancer with no diagnosis of pancreatic cancer who have been evaluated at a comprehensive cancer center. Descriptive statistics and Wilcoxon rank sum test and Fisher's exact test were used to assess univariate associations. Of the 132 respondents (72% response rate), 92 (70%) reported undergoing surveillance which was associated with older age (p = 0.001). Of which, 36% and 51% report that magnetic resonance imaging (MRI) or endoscopic ultrasound (EUS), respectively, were uncomfortable; 22% and 30% dread the next MRI or EUS, respectively. Of those who reported alcohol consumption (n = 88); 15% consumed 1 or more drinks daily and no alcohol consumption was associated with higher Impact of Event scale scores (p = 0.024). A total of six participants were currently smoking every day or some days. Participants reported high motivation to engage in heathy behaviours and 92% were interested in integrative therapies. In these select participants, most were engaging in pancreatic cancer surveillance, alcohol intake was moderate, and tobacco intake was minimal. Modifiable factors, such as experience and comfort with surveillance could be addressed. The sample is motivated to engage in behavioural health intervention.

7 Article A region-based gene association study combined with a leave-one-out sensitivity analysis identifies SMG1 as a pancreatic cancer susceptibility gene. 2019

Wong, Cavin / Chen, Fei / Alirezaie, Najmeh / Wang, Yifan / Cuggia, Adeline / Borgida, Ayelet / Holter, Spring / Lenko, Tatiana / Domecq, Celine / Anonymous4711019 / Petersen, Gloria M / Syngal, Sapna / Brand, Randall / Rustgi, Anil K / Cote, Michele L / Stoffel, Elena / Olson, Sara H / Roberts, Nicholas J / Akbari, Mohammad R / Majewski, Jacek / Klein, Alison P / Greenwood, Celia M T / Gallinger, Steven / Zogopoulos, George. ·The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. · The Goodman Cancer Research Centre of McGill University, Montreal, Quebec, Canada. · Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. · McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America. · Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical Schozol, Boston, Massachusetts, United States of America. · Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America. · Division of Gastroenterology, Departments of Medicine and Genetics, Pancreatic Cancer Translation Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America. · Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, United States of America. · Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America. · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, United States of America. · The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University, Baltimore, Maryland, United States of America. · Women's College Hospital Research Institute, Women's College Hospital, Toronto, Ontario, Canada. · Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. · Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Montreal, Quebec, Canada. · Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. · Gerald Bronfman Department of Oncology, and Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada. ·PLoS Genet · Pubmed #31469826.

ABSTRACT: Pancreatic adenocarcinoma (PC) is a lethal malignancy that is familial or associated with genetic syndromes in 10% of cases. Gene-based surveillance strategies for at-risk individuals may improve clinical outcomes. However, familial PC (FPC) is plagued by genetic heterogeneity and the genetic basis for the majority of FPC remains elusive, hampering the development of gene-based surveillance programs. The study was powered to identify genes with a cumulative pathogenic variant prevalence of at least 3%, which includes the most prevalent PC susceptibility gene, BRCA2. Since the majority of known PC susceptibility genes are involved in DNA repair, we focused on genes implicated in these pathways. We performed a region-based association study using the Mixed-Effects Score Test, followed by leave-one-out characterization of PC-associated gene regions and variants to identify the genes and variants driving risk associations. We evaluated 398 cases from two case series and 987 controls without a personal history of cancer. The first case series consisted of 109 patients with either FPC (n = 101) or PC at ≤50 years of age (n = 8). The second case series was composed of 289 unselected PC cases. We validated this discovery strategy by identifying known pathogenic BRCA2 variants, and also identified SMG1, encoding a serine/threonine protein kinase, to be significantly associated with PC following correction for multiple testing (p = 3.22x10-7). The SMG1 association was validated in a second independent series of 532 FPC cases and 753 controls (p<0.0062, OR = 1.88, 95%CI 1.17-3.03). We showed segregation of the c.4249A>G SMG1 variant in 3 affected relatives in a FPC kindred, and we found c.103G>A to be a recurrent SMG1 variant associating with PC in both the discovery and validation series. These results suggest that SMG1 is a novel PC susceptibility gene, and we identified specific SMG1 gene variants associated with PC risk.

8 Article Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer. 2019

Yurgelun, Matthew B / Chittenden, Anu B / Morales-Oyarvide, Vicente / Rubinson, Douglas A / Dunne, Richard F / Kozak, Margaret M / Qian, Zhi Rong / Welch, Marisa W / Brais, Lauren K / Da Silva, Annacarolina / Bui, Justin L / Yuan, Chen / Li, Tingting / Li, Wanwan / Masuda, Atsuhiro / Gu, Mancang / Bullock, Andrea J / Chang, Daniel T / Clancy, Thomas E / Linehan, David C / Findeis-Hosey, Jennifer J / Doyle, Leona A / Thorner, Aaron R / Ducar, Matthew D / Wollison, Bruce M / Khalaf, Natalia / Perez, Kimberly / Syngal, Sapna / Aguirre, Andrew J / Hahn, William C / Meyerson, Matthew L / Fuchs, Charles S / Ogino, Shuji / Hornick, Jason L / Hezel, Aram F / Koong, Albert C / Nowak, Jonathan A / Wolpin, Brian M. ·Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. matthew_yurgelun@dfci.harvard.edu. · Department of Medicine, Brigham & Women's Hospital, Boston, MA, USA. matthew_yurgelun@dfci.harvard.edu. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. · Department of Medicine, Brigham & Women's Hospital, Boston, MA, USA. · Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA. · Department of Radiation Oncology, Stanford Cancer Institute, Stanford, CA, USA. · Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. · Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. · Department of Surgery, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA. · Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA. · Department of Pathology, University of Rochester Medical Center, Rochester, NY, USA. · Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA. · Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA. · Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA. · Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·Genet Med · Pubmed #29961768.

ABSTRACT: PURPOSE: Germline variants in double-strand DNA damage repair (dsDDR) genes (e.g., BRCA1/2) predispose to pancreatic adenocarcinoma (PDAC) and may predict sensitivity to platinum-based chemotherapy and poly(ADP) ribose polymerase (PARP) inhibitors. We sought to determine the prevalence and significance of germline cancer susceptibility gene variants in PDAC with paired somatic and survival analyses. METHODS: Using a customized next-generation sequencing panel, germline/somatic DNA was analyzed from 289 patients with resected PDAC ascertained without preselection for high-risk features (e.g., young age, personal/family history). All identified variants were assessed for pathogenicity. Outcomes were analyzed using multivariable-adjusted Cox proportional hazards regression. RESULTS: We found that 28/289 (9.7%; 95% confidence interval [CI] 6.5-13.7%) patients carried pathogenic/likely pathogenic germline variants, including 21 (7.3%) dsDDR gene variants (3 BRCA1, 4 BRCA2, 14 other dsDDR genes [ATM, BRIP1, CHEK2, NBN, PALB2, RAD50, RAD51C]), 3 Lynch syndrome, and 4 other genes (APC p.I1307K, CDKN2A, TP53). Somatic sequencing and immunohistochemistry identified second hits in the tumor in 12/27 (44.4%) patients with germline variants (1 failed sequencing). Compared with noncarriers, patients with germline dsDDR gene variants had superior overall survival (hazard ratio [HR] 0.54; 95% CI 0.30-0.99; P = 0.05). CONCLUSION: Nearly 10% of PDAC patients harbor germline variants, although the majority lack somatic second hits, the therapeutic significance of which warrants further study.

9 Article Relationship between individual and family characteristics and psychosocial factors in persons with familial pancreatic cancer. 2018

Underhill, Meghan / Hong, Fangxin / Lawrence, Janette / Blonquist, Traci / Syngal, Sapna. ·The Phyllis F. Cantor Center for Research in Nursing and Patient Care Services, Dana-Farber Cancer Institute, Boston, MA, USA. · Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA. · Center for Cancer Risk Assessment, Massachusetts General Hospital, Boston, MA, USA. · GI Cancer Genetics and Prevention Program, Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. · Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA. ·Psychooncology · Pubmed #29570238.

ABSTRACT: OBJECTIVE: Describe relationships between self-reported personal demographics or familial characteristics and psychosocial outcomes (Patient Reported Outcome Measurement Information System Global Health, Impact of Event Scale-Revised [pancreatic cancer risk-related distress], cancer risk perception, and cancer worry) in participants with inherited or familial pancreatic cancer risk. METHODS: A multisite cross sectional survey of adults with elevated pancreatic cancer risk based on family history. All variables were summarized with descriptive statistics. To assess univariate associations, t test and chi-square/Fisher's exact test were used, and backward model selection was used in multivariable analysis. RESULTS: Respondents (N = 132) reported moderate to high frequency of cancer worry and 59.3% perceived a 50% or more perceived lifetime risk for pancreatic cancer, which far exceeds objective risk estimates. Cancer worry was associated with female gender (P = .03) and pancreatic cancer risk specific distress (P = .05). Higher-risk perception was associated with having a high school education or less (P = .001), higher distress (P = .02), and cancer worry (P = .008) and family cancer death experience (P = .02). Higher distress was associated with experience as a caregiver to a seriously ill family member in the past 5 years (P = .006). CONCLUSIONS: Individuals with inherited or familial pancreatic cancer risk experience cancer worry, distress, and have increased risk perception, particularly in the period following caring for a loved one with cancer. Routine evaluation of distress in this setting, as well as the development of supportive care resources, will help support patients living with risk for pancreatic cancer.

10 Article Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study. 2016

Childs, Erica J / Chaffee, Kari G / Gallinger, Steven / Syngal, Sapna / Schwartz, Ann G / Cote, Michele L / Bondy, Melissa L / Hruban, Ralph H / Chanock, Stephen J / Hoover, Robert N / Fuchs, Charles S / Rider, David N / Amundadottir, Laufey T / Stolzenberg-Solomon, Rachael / Wolpin, Brian M / Risch, Harvey A / Goggins, Michael G / Petersen, Gloria M / Klein, Alison P. ·Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota. · Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada. · Population Sciences Division, Dana-Farber Cancer Institute, and Gastroenterology Division, Brigham and Women's Hospital, Boston, Massachusetts. · Department of Oncology, Karmanos Cancer Institute and Wayne State University, Detroit, Michigan. · Baylor College of Medicine, Dan L. Duncan Cancer Center, Houston, Texas. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland. aklein1@jhmi.edu. ·Cancer Epidemiol Biomarkers Prev · Pubmed #27197284.

ABSTRACT: Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13-1.63; P = 9.29 × 10(-4); 7p13, rs17688601: OR = 0.76; 95% CI, 0.63-0.93; P = 6.59 × 10(-3)). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P < 5 × 10(-5)) to pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 25(7); 1185-91. ©2016 AACR.

11 Article Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer. 2016

Roberts, Nicholas J / Norris, Alexis L / Petersen, Gloria M / Bondy, Melissa L / Brand, Randall / Gallinger, Steven / Kurtz, Robert C / Olson, Sara H / Rustgi, Anil K / Schwartz, Ann G / Stoffel, Elena / Syngal, Sapna / Zogopoulos, George / Ali, Syed Z / Axilbund, Jennifer / Chaffee, Kari G / Chen, Yun-Ching / Cote, Michele L / Childs, Erica J / Douville, Christopher / Goes, Fernando S / Herman, Joseph M / Iacobuzio-Donahue, Christine / Kramer, Melissa / Makohon-Moore, Alvin / McCombie, Richard W / McMahon, K Wyatt / Niknafs, Noushin / Parla, Jennifer / Pirooznia, Mehdi / Potash, James B / Rhim, Andrew D / Smith, Alyssa L / Wang, Yuxuan / Wolfgang, Christopher L / Wood, Laura D / Zandi, Peter P / Goggins, Michael / Karchin, Rachel / Eshleman, James R / Papadopoulos, Nickolas / Kinzler, Kenneth W / Vogelstein, Bert / Hruban, Ralph H / Klein, Alison P. ·Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. Ludwig Center and the Howard Hughes Medical Institute, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. vogelbe@jhmi.edu nrobert8@jhmi.edu kinzlke@jhmi.edu rhruban@jhmi.edu aklein1@jhmi.edu. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. · Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas. · Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. · Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. · Division of Gastroenterology, Departments of Medicine and Genetics, Pancreatic Cancer Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. · Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan. · Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. · Population Sciences Division, Dana-Farber Cancer Institute, and Gastroenterology Division, Brigham and Women's Hospital, Boston, Massachusetts. · The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada. · Department of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland. · Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Memorial Sloan Kettering Cancer Center, New York, New York. · Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York. · Ludwig Center and the Howard Hughes Medical Institute, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York. inGenious Targeting Laboratory, Ronkonkoma, New York. · Department of Psychiatry, University of Iowa, Iowa City, Iowa. · Division of Gastroenterology, Departments of Medicine and Genetics, Pancreatic Cancer Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Medicine, University of Michigan, Ann Arbor, Michigan. · Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. Department of Medicine, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Ludwig Center and the Howard Hughes Medical Institute, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. vogelbe@jhmi.edu nrobert8@jhmi.edu kinzlke@jhmi.edu rhruban@jhmi.edu aklein1@jhmi.edu. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. vogelbe@jhmi.edu nrobert8@jhmi.edu kinzlke@jhmi.edu rhruban@jhmi.edu aklein1@jhmi.edu. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland. Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. vogelbe@jhmi.edu nrobert8@jhmi.edu kinzlke@jhmi.edu rhruban@jhmi.edu aklein1@jhmi.edu. ·Cancer Discov · Pubmed #26658419.

ABSTRACT: SIGNIFICANCE: The genetic basis of disease susceptibility in the majority of patients with familial pancreatic cancer is unknown. We whole genome sequenced 638 patients with familial pancreatic cancer and demonstrate that the genetic underpinning of inherited pancreatic cancer is highly heterogeneous. This has significant implications for the management of patients with familial pancreatic cancer.

12 Article Patient experiences living with pancreatic cancer risk. 2015

Underhill, Meghan / Berry, Donna / Dalton, Emily / Schienda, Jaclyn / Syngal, Sapna. ·Dana-Farber Cancer Institute, Boston, MA USA. · Ambry Genetics, (previously Dana-Farber Cancer Institute), Boston, MA USA. ·Hered Cancer Clin Pract · Pubmed #26029287.

ABSTRACT: BACKGROUND: Pancreatic cancer (PancCa) is recognized as a component of many well-described hereditary cancer syndromes. Minimal research has focused on patient needs and experiences living with this risk. PURPOSE: To understand the meaning and experience of living with familial PancCa risk and to explore experiences related to screening and prevention of PancCa. METHODS: Participants underwent semi-structured, in-depth interviews. Adults without PancCa and who met familial or hereditary risk criteria were eligible. Thematic analysis was completed on the transcripts in order to identify patterns, consistencies, and differences. Narrative review of existing literature related to women living with hereditary breast and ovarian cancer (HBOC) risk was completed to explore similarities and differences between published findings and our current findings. RESULTS: Nineteen individuals (9 male, 10 female) participated. Major themes addressed participants' family experiences with PancCa and PancCa death and the associated grief from the experiences. Family experiences impacted how participants interpreted and approached their own cancer risk and participated in the cancer screening program. Participants wanted to control their cancer risk and sought information and resources to prevent PancCa or PancCa related death. Distress related to risk was not described as constant but occurred around salient time points. CONCLUSION & FUTURE IMPLICATIONS: Study results begin to describe the lived experience of individuals with PancCa risk. Through this research we have uncovered important variables to further understand, measure, and intervene upon in future research. Distress related to risk was not described as ongoing, but occurred around specific and salient time points that brought risk to the forefront. Individuals with familial PancCa risk may have a unique experience compared to other hereditary cancer syndromes due to the high mortality of the disease and uncertainty related to prevention and early detection outcomes.

13 Article Linear-array EUS improves detection of pancreatic lesions in high-risk individuals: a randomized tandem study. 2015

Shin, Eun Ji / Topazian, Mark / Goggins, Michael G / Syngal, Sapna / Saltzman, John R / Lee, Jeffrey H / Farrell, James J / Canto, Marcia I. ·Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. · Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Gastroenterology, Hepatology, and Nutrition, MD Anderson Cancer Center, Houston, Texas, USA. · Section of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut, USA. ·Gastrointest Endosc · Pubmed #25930097.

ABSTRACT: BACKGROUND: Studies comparing linear and radial EUS for the detection of pancreatic lesions in an asymptomatic population with increased risk for pancreatic cancer are lacking. OBJECTIVES: To compare pancreatic lesion detection rates between radial and linear EUS and to determine the incremental diagnostic yield of a second EUS examination. DESIGN: Randomized controlled tandem study. SETTING: Five academic centers in the United States. PATIENTS: Asymptomatic high-risk individuals (HRIs) for pancreatic cancer undergoing screening EUS. INTERVENTIONS: Linear and radial EUS performed in randomized order. MAIN OUTCOME MEASUREMENTS: Pancreatic lesion detection rate by type of EUS, miss rate of 1 EUS examination, and incremental diagnostic yield of a second EUS examination (second-pass effect). RESULTS: Two hundred seventy-eight HRIs were enrolled, mean age 56 years (43.2%), and 90% were familial pancreatic cancer relatives. Two hundred twenty-four HRIs underwent tandem radial and linear EUS. When we used per-patient analysis, the overall prevalence of any pancreatic lesion was 45%. Overall, 16 of 224 HRIs (7.1%) had lesions missed during the initial EUS that were detected by the second EUS examination. The per-patient lesion miss rate was significantly greater for radial followed by linear EUS (9.8%) than for linear followed by radial EUS (4.5%) (P = .03). When we used per-lesion analysis, 73 of 109 lesions (67%) were detected by radial EUS and 99 of 120 lesions (82%) were detected by linear EUS (P < .001) during the first examination. The overall miss rate for a pancreatic lesion after 1 EUS examination was 47 of 229 (25%). The miss rate was significantly lower for linear EUS compared with radial EUS (17.5% vs 33.0%, P = .007). LIMITATIONS: Most detected pancreatic lesions were not confirmed by pathology. CONCLUSION: Linear EUS detects more pancreatic lesions than radial EUS. There was a "second-pass effect" with additional lesions detected with a second EUS examination. This effect was significantly greater when linear EUS was used after an initial radial EUS examination.

14 Article Incremental value of secretin-enhanced magnetic resonance cholangiopancreatography in detecting ductal communication in a population with high prevalence of small pancreatic cysts. 2015

Rastegar, Neda / Matteoni-Athayde, Luciana G / Eng, John / Takahashi, Naoki / Tamm, Eric P / Mortele, Koenraad J / Syngal, Sapna / Margolis, Daniel / Lennon, Anne Marie / Wolfgang, Christopher L / Fishman, Elliot K / Hruban, Ralph H / Goggins, Michael / Canto, Marcia I / Kamel, Ihab R. ·Departments of Medicine (Gastroenterology) and Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, United States. · Mayo Clinic, United States. · MD Anderson Cancer Center, United States. · Beth Israel Deaconess Medical Center, United States. · Dana Farber Cancer Institute, United States. · University of California, Los Angeles, United States. · Departments of Medicine (Gastroenterology) and Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, United States. Electronic address: ikamel@jhmi.edu. ·Eur J Radiol · Pubmed #25619503.

ABSTRACT: PURPOSE: We investigated the incremental diagnostic yield of S-MRCP in a population with high prevalence of small pancreatic cysts. METHODS: Standard MRCP protocol was performed with and without secretin using 1.5 T units in subjects undergoing pancreatic screening because of a strong family history of pancreatic cancer as part of the multicenter Cancer of the Pancreas Screening-3 trial (CAPS 3). All studies were reviewed prospectively by two independent readers who recorded the presence and number of pancreatic cysts, the presence of visualized ductal communication before and after secretin, and the degree of confidence in the diagnoses. RESULT: Of 202 individuals enrolled (mean age 56 years, 46% males), 93 (46%) had pancreatic cysts detected by MRCP, and 64 of the 93 had pre-and post-secretin MRCP images available for comparison. Data from the 128 readings show that 6 (6/128=4.7%) had ductal communication visualized only on the secretin studies compared to pre-secretin studies (odds ratio 1.28, p=0.04). In addition, there was a statistically significant increase in confidence in reporting ductal communication after secretin compared to before secretin (p<0.0005). CONCLUSION: At 1.5 T MRI, the use of secretin can improve the visualization of ductal communication of cystic pancreatic lesions.

15 Article KRAS and guanine nucleotide-binding protein mutations in pancreatic juice collected from the duodenum of patients at high risk for neoplasia undergoing endoscopic ultrasound. 2015

Eshleman, James R / Norris, Alexis L / Sadakari, Yoshihiko / Debeljak, Marija / Borges, Michael / Harrington, Colleen / Lin, Elaine / Brant, Aaron / Barkley, Thomas / Almario, J Alejandro / Topazian, Mark / Farrell, James / Syngal, Sapna / Lee, Jeffrey H / Yu, Jun / Hruban, Ralph H / Kanda, Mitsuro / Canto, Marcia Irene / Goggins, Michael. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. Electronic address: jeshlem@jhmi.edu. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Mayo Clinic, Rochester, Minnesota. · Dana Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Yale University, New Haven, Connecticut. · MD Anderson Cancer Center, Houston, Texas. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. Electronic address: mgoggins@jhmi.edu. ·Clin Gastroenterol Hepatol · Pubmed #25481712.

ABSTRACT: BACKGROUND & AIMS: Pancreatic imaging can identify neoplastic cysts but not microscopic neoplasms. Mutation analysis of pancreatic fluid after secretin stimulation might identify microscopic neoplasias in the pancreatic duct system. We determined the prevalence of mutations in KRAS and guanine nucleotide-binding protein α-stimulating genes in pancreatic juice from subjects undergoing endoscopic ultrasound for suspected pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms, or pancreatic adenocarcinoma. METHODS: Secretin-stimulated juice samples were collected from the duodenum of 272 subjects enrolled in Cancer of the Pancreas Screening studies; 194 subjects were screened because of a family history of, or genetic predisposition to, pancreatic cancer, and 78 subjects were evaluated for pancreatic cancer (n = 30) or other disorders (controls: pancreatic cysts, pancreatitis, or normal pancreata, n = 48). Mutations were detected by digital high-resolution melt-curve analysis and pyrosequencing. The number of replicates containing a mutation determined the mutation score. RESULTS: KRAS mutations were detected in pancreatic juice from larger percentages of subjects with pancreatic cancer (73%) or undergoing cancer screening (50%) than controls (19%) (P = .0005). A greater proportion of patients with pancreatic cancer had at least 1 KRAS mutation detected 3 or more times (47%) than screened subjects (21%) or controls (6%, P = .002). Among screened subjects, mutations in KRAS (but not guanine nucleotide-binding protein α-stimulating) were found in similar percentages of patients with or without pancreatic cysts. However, a greater proportion of patients older than age 50 years had KRAS mutations (54.6%) than younger patients (36.3%) (P = .032); the older subjects also had more mutations in KRAS (P = .02). CONCLUSIONS: Mutations in KRAS are detected in pancreatic juice from the duodenum of 73% of patients with pancreatic cancer, and 50% of asymptomatic individuals with a high risk for pancreatic cancer. However, KRAS mutations were detected in pancreatic juice from 19% of controls. Mutations detected in individuals without pancreatic abnormalities, based on imaging analyses, likely arise from small pancreatic intraepithelial neoplasia lesions. ClinicalTrials.gov no: NCT00438906 and NCT00714701.

16 Article BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study. 2015

Zhen, David B / Rabe, Kari G / Gallinger, Steven / Syngal, Sapna / Schwartz, Ann G / Goggins, Michael G / Hruban, Ralph H / Cote, Michele L / McWilliams, Robert R / Roberts, Nicholas J / Cannon-Albright, Lisa A / Li, Donghui / Moyes, Kelsey / Wenstrup, Richard J / Hartman, Anne-Renee / Seminara, Daniela / Klein, Alison P / Petersen, Gloria M. ·Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Divison of General Surgery, University of Toronto, Toronto, Ontario, Canada. · Population Sciences Division, Dana-Farber Cancer Institute, and Gastroenterology Division, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Oncology, Karmanos Cancer Institute and Wayne State University, Detroit, Michigan, USA. · The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA. · Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA. · 1] The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA [2] Ludwig Center for Cancer Genetics, Johns Hopkins University, Baltimore, Maryland, USA. · Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, USA. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Myriad Genetic Laboratories, Inc., Salt Lake City, Utah, USA. · Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, USA. ·Genet Med · Pubmed #25356972.

ABSTRACT: PURPOSE: Familial pancreatic cancer kindreds contain at least two affected first-degree relatives. Comprehensive data are needed to assist clinical risk assessment and genetic testing. METHODS: Germ-line DNA samples from 727 unrelated probands with positive family history (521 met criteria for familial pancreatic cancer) were tested in compliance with the Clinical Laboratory Improvement Amendments for mutations in BRCA1 and BRCA2 (including analysis of deletions and rearrangements), PALB2, and CDKN2A. We compared prevalence of deleterious mutations between familial pancreatic cancer probands and nonfamilial pancreatic cancer probands (kindreds containing at least two affected biological relatives, but not first-degree relatives). We also examined the impact of family history on breast and ovarian cancers and melanoma. RESULTS: Prevalence of deleterious mutations (excluding variants of unknown significance) among familial pancreatic cancer probands was: BRCA1, 1.2%; BRCA2, 3.7%; PALB2, 0.6%; and CDKN2A, 2.5%. Four novel deleterious mutations were detected. Familial pancreatic cancer probands carry more mutations in the four genes (8.0%) than nonfamilial pancreatic cancer probands (3.5%) (odds ratio: 2.40; 95% confidence interval: 1.06-5.44; P = 0.03). The probability of testing positive for deleterious mutations in any of the four genes ranges up to 10.4%, depending on family history of cancers. BRCA2 and CDKN2A account for the majority of mutations in familial pancreatic cancer. CONCLUSION: Genetic testing of multiple relevant genes in probands with a positive family history is warranted, particularly for familial pancreatic cancer.

17 Article Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. 2013

Kanda, Mitsuro / Sadakari, Yoshihiko / Borges, Michael / Topazian, Mark / Farrell, James / Syngal, Sapna / Lee, Jeffrey / Kamel, Ihab / Lennon, Anne Marie / Knight, Spencer / Fujiwara, Sho / Hruban, Ralph H / Canto, Marcia Irene / Goggins, Michael. ·Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. ·Clin Gastroenterol Hepatol · Pubmed #23200980.

ABSTRACT: BACKGROUND & AIMS: Imaging tests can identify patients with pancreatic neoplastic cysts but not microscopic dysplasia. We investigated whether mutant TP53 can be detected in duodenal samples of secretin-stimulated pancreatic juice, and whether this assay can be used to screen for high-grade dysplasia and invasive pancreatic cancer. METHODS: We determined the prevalence of mutant TP53 in microdissected pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and invasive adenocarcinomas. TP53 mutations were quantified by digital high-resolution melt-curve analysis and sequencing of secretin-stimulated pancreatic juice samples, collected from duodena of 180 subjects enrolled in Cancer of the Pancreas Screening trials; patients were enrolled because of familial and/or inherited predisposition to pancreatic cancer, or as controls. RESULTS: TP53 mutations were identified in 9.1% of intermediate-grade IPMNs (2 of 22), 17.8% of PanIN-2 (8 of 45), 38.1% of high-grade IPMNs (8 of 21), 47.6% of PanIN-3 (10 of 21), and 75% of invasive pancreatic adenocarcinomas (15 of 20); no TP53 mutations were found in PanIN-1 lesions or low-grade IPMNs. TP53 mutations were detected in duodenal samples of pancreatic juice from 29 of 43 patients with pancreatic ductal adenocarcinoma (67.4% sensitivity; 95% confidence interval, 0.52-0.80) and 4 of 8 patients with high-grade lesions (PanIN-3 and high-grade IPMN). No TP53 mutations were identified in samples from 58 controls or 55 screened individuals without evidence of advanced lesions. CONCLUSIONS: We detected mutant TP53 in secretin-stimulated pancreatic juice samples collected from duodena of patients with high-grade dysplasia or invasive pancreatic cancer. Tests for mutant TP53 might be developed to improve the diagnosis of and screening for pancreatic cancer and high-grade dysplasia. Clinical Trial numbers: NCT00438906 and NCT00714701.

18 Article Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts. 2013

Kanda, Mitsuro / Knight, Spencer / Topazian, Mark / Syngal, Sapna / Farrell, James / Lee, Jeffrey / Kamel, Ihab / Lennon, Anne Marie / Borges, Michael / Young, Angela / Fujiwara, Sho / Seike, Junro / Eshleman, James / Hruban, Ralph H / Canto, Marcia Irene / Goggins, Michael. ·Johns Hopkins Medical Institutions, Department of Pathology, Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, 1550 Orleans Street, Baltimore, MD 21231, USA. ·Gut · Pubmed #22859495.

ABSTRACT: OBJECTIVE: Pancreatic cysts are commonly detected in patients undergoing pancreatic imaging. Better approaches are needed to characterise these lesions. In this study we evaluated the utility of detecting mutant DNA in secretin-stimulated pancreatic juice. DESIGN: Secretin-stimulated pancreatic juice was collected from the duodenum of 291 subjects enrolled in Cancer of the Pancreas Screening trials at five US academic medical centres. The study population included subjects with a familial predisposition to pancreatic cancer who underwent pancreatic screening, and disease controls with normal pancreata, chronic pancreatitis, sporadic intraductal papillary mucinous neoplasm (IPMN) or other neoplasms. Somatic GNAS mutations (reported prevalence ≈ 66% of IPMNs) were measured using digital high-resolution melt-curve analysis and pyrosequencing. RESULTS: GNAS mutations were detected in secretin-stimulated pancreatic juice samples of 50 of 78 familial and sporadic cases of IPMN(s) (64.1%), 15 of 33 (45.5%) with only diminutive cysts (<5 mm), but none of 57 disease controls. GNAS mutations were also detected in five of 123 screened subjects without a pancreatic cyst. Among 97 subjects who had serial pancreatic evaluations, GNAS mutations detected in baseline juice samples predicted subsequent emergence or increasing size of pancreatic cysts. CONCLUSION: Duodenal collections of secretin-stimulated pancreatic juice from patients with IPMNs have a similar prevalence of mutant GNAS to primary IPMNs, indicating that these samples are an excellent source of mutant DNA from the pancreas. The detection of GNAS mutations before an IPMN is visible suggests that analysis of pancreatic juice has the potential to help in the risk stratification and surveillance of patients undergoing pancreatic screening.

19 Article Identification of germline genomic copy number variation in familial pancreatic cancer. 2012

Al-Sukhni, Wigdan / Joe, Sarah / Lionel, Anath C / Zwingerman, Nora / Zogopoulos, George / Marshall, Christian R / Borgida, Ayelet / Holter, Spring / Gropper, Aaron / Moore, Sara / Bondy, Melissa / Klein, Alison P / Petersen, Gloria M / Rabe, Kari G / Schwartz, Ann G / Syngal, Sapna / Scherer, Stephen W / Gallinger, Steven. ·Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada. wigdan.al.sukhni@utoronto.ca ·Hum Genet · Pubmed #22665139.

ABSTRACT: Adenocarcinoma of the pancreas is a significant cause of cancer mortality, and up to 10 % of cases appear to be familial. Heritable genomic copy number variants (CNVs) can modulate gene expression and predispose to disease. Here, we identify candidate predisposition genes for familial pancreatic cancer (FPC) by analyzing germline losses or gains present in one or more high-risk patients and absent in a large control group. A total of 120 FPC cases and 1,194 controls were genotyped on the Affymetrix 500K array, and 36 cases and 2,357 controls were genotyped on the Affymetrix 6.0 array. Detection of CNVs was performed by multiple computational algorithms and partially validated by quantitative PCR. We found no significant difference in the germline CNV profiles of cases and controls. A total of 93 non-redundant FPC-specific CNVs (53 losses and 40 gains) were identified in 50 cases, each CNV present in a single individual. FPC-specific CNVs overlapped the coding region of 88 RefSeq genes. Several of these genes have been reported to be differentially expressed and/or affected by copy number alterations in pancreatic adenocarcinoma. Further investigation in high-risk subjects may elucidate the role of one or more of these genes in genetic predisposition to pancreatic cancer.

20 Article ATM mutations in patients with hereditary pancreatic cancer. 2012

Roberts, Nicholas J / Jiao, Yuchen / Yu, Jun / Kopelovich, Levy / Petersen, Gloria M / Bondy, Melissa L / Gallinger, Steven / Schwartz, Ann G / Syngal, Sapna / Cote, Michele L / Axilbund, Jennifer / Schulick, Richard / Ali, Syed Z / Eshleman, James R / Velculescu, Victor E / Goggins, Michael / Vogelstein, Bert / Papadopoulos, Nickolas / Hruban, Ralph H / Kinzler, Kenneth W / Klein, Alison P. ·Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland, USA. ·Cancer Discov · Pubmed #22585167.

ABSTRACT: SIGNIFICANCE: The genes responsible for the majority of cases of familial pancreatic ductal adenocarcinoma are unknown. We here identify ATM as a predisposition gene for pancreatic ductal adenocarcinoma. Our results have important implications for the management of patients in affected families and illustrate the power of genome-wide sequencing to identify the basis of familial cancer syndromes.

21 Article Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. 2012

Canto, Marcia Irene / Hruban, Ralph H / Fishman, Elliot K / Kamel, Ihab R / Schulick, Richard / Zhang, Zhe / Topazian, Mark / Takahashi, Naoki / Fletcher, Joel / Petersen, Gloria / Klein, Alison P / Axilbund, Jennifer / Griffin, Constance / Syngal, Sapna / Saltzman, John R / Mortele, Koenraad J / Lee, Jeffrey / Tamm, Eric / Vikram, Raghunandan / Bhosale, Priya / Margolis, Daniel / Farrell, James / Goggins, Michael / Anonymous3280715. ·Department of Medicine (Division of Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA. mcanto@jhmi.edu ·Gastroenterology · Pubmed #22245846.

ABSTRACT: BACKGROUND & AIMS: The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, noninvasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRIs). METHODS: We screened 225 asymptomatic adult HRIs at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS: Ninety-two of 216 HRIs (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n = 5) by any of the imaging modalities. Fifty-one of the 84 HRIs with a cyst (60.7%) had multiple lesions, typically small (mean, 0.55 cm; range, 2-39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects younger than 50 years old, 34% of subjects 50-59 years old, and 53% of subjects 60-69 years old (P < .0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRIs, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRIs (82 intraductal papillary mucinous neoplasms and 3 pancreatic endocrine tumors). Three of 5 HRIs who underwent pancreatic resection had high-grade dysplasia in less than 3 cm intraductal papillary mucinous neoplasms and in multiple intraepithelial neoplasias. CONCLUSIONS: Screening of asymptomatic HRIs frequently detects small pancreatic cysts, including curable, noninvasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT.