Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Iris Selander
Based on 3 articles published since 2009
(Why 3 articles?)
||||

Between 2009 and 2019, Iris Selander wrote the following 3 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Association of Distinct Mutational Signatures With Correlates of Increased Immune Activity in Pancreatic Ductal Adenocarcinoma. 2017

Connor, Ashton A / Denroche, Robert E / Jang, Gun Ho / Timms, Lee / Kalimuthu, Sangeetha N / Selander, Iris / McPherson, Treasa / Wilson, Gavin W / Chan-Seng-Yue, Michelle A / Borozan, Ivan / Ferretti, Vincent / Grant, Robert C / Lungu, Ilinca M / Costello, Eithne / Greenhalf, William / Palmer, Daniel / Ghaneh, Paula / Neoptolemos, John P / Buchler, Markus / Petersen, Gloria / Thayer, Sarah / Hollingsworth, Michael A / Sherker, Alana / Durocher, Daniel / Dhani, Neesha / Hedley, David / Serra, Stefano / Pollett, Aaron / Roehrl, Michael H A / Bavi, Prashant / Bartlett, John M S / Cleary, Sean / Wilson, Julie M / Alexandrov, Ludmil B / Moore, Malcolm / Wouters, Bradly G / McPherson, John D / Notta, Faiyaz / Stein, Lincoln D / Gallinger, Steven. ·PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada2Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada3Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada4Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada4Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada5Department of Statistical Science, University of Toronto, Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada6Genome Technologies Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada2Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · Transformative Pathology, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. · University of Liverpool, Liverpool, England. · Heidelberg University Hospital, Heidelberg, Germany. · Mayo Clinic, Rochester, Minnesota. · Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts. · University of Nebraska Medical Centre, Omaha, Nebraska. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada13Molecular Genetics Department, University of Toronto, Toronto, Ontario, Canada. · Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. · Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, Ontario, Canada. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada15Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada15Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada16Department of Pathology, University Health Network, Toronto, Ontario, Canada17Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada18BioSpecimen Sciences Program, University Health Network, Toronto, Ontario, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada3Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, Ontario, Canada. · Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory, Los Alamos, New Mexico20Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico. · Department of Pathology, University Health Network, Toronto, Ontario, Canada. · Genome Technologies Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada17Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. · Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada13Molecular Genetics Department, University of Toronto, Toronto, Ontario, Canada. ·JAMA Oncol · Pubmed #27768182.

ABSTRACT: Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium. The discovery cohort comprised 160 PDAC cases from 154 patients (148 primary; 12 metastases) that underwent tumor enrichment prior to whole-genome and RNA sequencing. The replication cohort comprised 95 primary PDAC cases that underwent whole-genome sequencing and expression microarray on bulk biospecimens. Main Outcomes and Measures: Somatic mutations accumulate from sequence-specific processes creating signatures detectable by DNA sequencing. Using nonnegative matrix factorization, we measured the contribution of each signature to carcinogenesis, and used hierarchical clustering to subtype each cohort. We examined expression of antitumor immunity genes across subtypes to uncover biomarkers predictive of response to systemic therapies. Results: The discovery cohort was 53% male (n = 79) and had a median age of 67 (interquartile range, 58-74) years. The replication cohort was 50% male (n = 48) and had a median age of 68 (interquartile range, 60-75) years. Five predominant mutational subtypes were identified that clustered PDAC into 4 major subtypes: age related, double-strand break repair, mismatch repair, and 1 with unknown etiology (signature 8). These were replicated and validated. Signatures were faithfully propagated from primaries to matched metastases, implying their stability during carcinogenesis. Twelve of 27 (45%) double-strand break repair cases lacked germline or somatic events in canonical homologous recombination genes-BRCA1, BRCA2, or PALB2. Double-strand break repair and mismatch repair subtypes were associated with increased expression of antitumor immunity, including activation of CD8-positive T lymphocytes (GZMA and PRF1) and overexpression of regulatory molecules (cytotoxic T-lymphocyte antigen 4, programmed cell death 1, and indolamine 2,3-dioxygenase 1), corresponding to higher frequency of somatic mutations and tumor-specific neoantigens. Conclusions and Relevance: Signature-based subtyping may guide personalized therapy of PDAC in the context of biomarker-driven prospective trials.

2 Article Candidate DNA repair susceptibility genes identified by exome sequencing in high-risk pancreatic cancer. 2016

Smith, Alyssa L / Alirezaie, Najmeh / Connor, Ashton / Chan-Seng-Yue, Michelle / Grant, Robert / Selander, Iris / Bascuñana, Claire / Borgida, Ayelet / Hall, Anita / Whelan, Thomas / Holter, Spring / McPherson, Treasa / Cleary, Sean / Petersen, Gloria M / Omeroglu, Atilla / Saloustros, Emmanouil / McPherson, John / Stein, Lincoln D / Foulkes, William D / Majewski, Jacek / Gallinger, Steven / Zogopoulos, George. ·Research Institute of the McGill University Health Centre, 1001 Décarie Boulevard, Montreal, QC, Canada H4A 3J1; Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montreal, QC, Canada H3A 1A3. · McGill University and Genome Quebec Innovation Centre, 740 Dr. Penfield Avenue, Montreal, QC, Canada H3A 0G1. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5; MaRS Centre, Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, Canada M5G 0A3. · MaRS Centre, Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, Canada M5G 0A3. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5; Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, 60 Murray Street, Toronto, ON, Canada M5T 3H7. · Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. · Department of Pathology, McGill University Health Centre, 1001 Décarie Boulevard, Montreal, QC, Canada H4A 3J1. · Department of Medical Oncology, Hereditary Cancer Clinic, University Hospital of Heraklion, Voutes, Heraklion 71110, Greece. · Program in Cancer Genetics, Departments of Oncology and Human Genetics, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 Côte-Ste-Catherine Road, Montreal, QC, Canada H3T 1E2. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5; MaRS Centre, Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, Canada M5G 0A3; Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, 60 Murray Street, Toronto, ON, Canada M5T 3H7. Electronic address: steven.gallinger@uhn.ca. · Research Institute of the McGill University Health Centre, 1001 Décarie Boulevard, Montreal, QC, Canada H4A 3J1; Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montreal, QC, Canada H3A 1A3; Program in Cancer Genetics, Departments of Oncology and Human Genetics, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 Côte-Ste-Catherine Road, Montreal, QC, Canada H3T 1E2. Electronic address: george.zogopoulos@mcgill.ca. ·Cancer Lett · Pubmed #26546047.

ABSTRACT: The genetic basis underlying the majority of hereditary pancreatic adenocarcinoma (PC) is unknown. Since DNA repair genes are widely implicated in gastrointestinal malignancies, including PC, we hypothesized that there are novel DNA repair PC susceptibility genes. As germline DNA repair gene mutations may lead to PC subtypes with selective therapeutic responses, we also hypothesized that there is an overall survival (OS) difference in mutation carriers versus non-carriers. We therefore interrogated the germline exomes of 109 high-risk PC cases for rare protein-truncating variants (PTVs) in 513 putative DNA repair genes. We identified PTVs in 41 novel genes among 36 kindred. Additional genetic evidence for causality was obtained for 17 genes, with FAN1, NEK1 and RHNO1 emerging as the strongest candidates. An OS difference was observed for carriers versus non-carriers of PTVs with early stage (≤IIB) disease. This adverse survival trend in carriers with early stage disease was also observed in an independent series of 130 PC cases. We identified candidate DNA repair PC susceptibility genes and suggest that carriers of a germline PTV in a DNA repair gene with early stage disease have worse survival.

3 Article Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer. 2015

Grant, Robert C / Selander, Iris / Connor, Ashton A / Selvarajah, Shamini / Borgida, Ayelet / Briollais, Laurent / Petersen, Gloria M / Lerner-Ellis, Jordan / Holter, Spring / Gallinger, Steven. ·Ontario Institute for Cancer Research, Canada; Department of Medicine, University of Toronto, Canada. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Canada. · Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada. · Laboratory Medicine and Pathobiology, University of Toronto, Canada. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. · Ontario Institute for Cancer Research, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Canada; Pathology and Laboratory Medicine, Mount Sinai Hospital, Canada. · Ontario Institute for Cancer Research, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada. Electronic address: steven.gallinger@uhn.on.ca. ·Gastroenterology · Pubmed #25479140.

ABSTRACT: BACKGROUND & AIMS: We investigated the prevalence of germline mutations in APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53 in patients with pancreatic cancer. METHODS: The Ontario Pancreas Cancer Study enrolls consenting participants with pancreatic cancer from a province-wide electronic pathology database; 708 probands were enrolled from April 2003 through August 2012. To improve the precision of BRCA2 prevalence estimates, 290 probands were selected from 3 strata, based on family history of breast and/or ovarian cancer, pancreatic cancer, or neither. Germline DNA was analyzed by next-generation sequencing using a custom multiple-gene panel. Mutation prevalence estimates were calculated from the sample for the entire cohort. RESULTS: Eleven pathogenic mutations were identified: 3 in ATM, 1 in BRCA1, 2 in BRCA2, 1 in MLH1, 2 in MSH2, 1 in MSH6, and 1 in TP53. The prevalence of mutations in all 13 genes was 3.8% (95% confidence interval, 2.1%-5.6%). Carrier status was associated significantly with breast cancer in the proband or first-degree relative (P < .01), and with colorectal cancer in the proband or first-degree relative (P < .01), but not family history of pancreatic cancer, age at diagnosis, or stage at diagnosis. Of patients with a personal or family history of breast and colorectal cancer, 10.7% (95% confidence interval, 4.4%-17.0%) and 11.1% (95% confidence interval, 3.0%-19.1%) carried pathogenic mutations, respectively. CONCLUSIONS: A small but clinically important proportion of pancreatic cancer is associated with mutations in known predisposition genes. The heterogeneity of mutations identified in this study shows the value of using a multiple-gene panel in pancreatic cancer.