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Pancreatic Neoplasms: HELP
Articles by David L. Masica
Based on 3 articles published since 2010
(Why 3 articles?)
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Between 2010 and 2020, David Masica wrote the following 3 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Intraductal Papillary Mucinous Neoplasms Arise From Multiple Independent Clones, Each With Distinct Mutations. 2019

Fischer, Catherine G / Beleva Guthrie, Violeta / Braxton, Alicia M / Zheng, Lily / Wang, Pei / Song, Qianqian / Griffin, James F / Chianchiano, Peter E / Hosoda, Waki / Niknafs, Noushin / Springer, Simeon / Dal Molin, Marco / Masica, David / Scharpf, Robert B / Thompson, Elizabeth D / He, Jin / Wolfgang, Christopher L / Hruban, Ralph H / Roberts, Nicholas J / Lennon, Anne Marie / Jiao, Yuchen / Karchin, Rachel / Wood, Laura D. ·Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. · State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. · Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Medicine, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: karchin@jhu.edu. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: ldwood@jhmi.edu. ·Gastroenterology · Pubmed #31175866.

ABSTRACT: BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are lesions that can progress to invasive pancreatic cancer and constitute an important system for studies of pancreatic tumorigenesis. We performed comprehensive genomic analyses of entire IPMNs to determine the diversity of somatic mutations in genes that promote tumorigenesis. METHODS: We microdissected neoplastic tissues from 6-24 regions each of 20 resected IPMNs, resulting in 227 neoplastic samples that were analyzed by capture-based targeted sequencing. Somatic mutations in genes associated with pancreatic tumorigenesis were assessed across entire IPMN lesions, and the resulting data were supported by evolutionary modeling, whole-exome sequencing, and in situ detection of mutations. RESULTS: We found a high prevalence of heterogeneity among mutations in IPMNs. Heterogeneity in mutations in KRAS and GNAS was significantly more prevalent in IPMNs with low-grade dysplasia than in IPMNs with high-grade dysplasia (P < .02). Whole-exome sequencing confirmed that IPMNs contained multiple independent clones, each with distinct mutations, as originally indicated by targeted sequencing and evolutionary modeling. We also found evidence for convergent evolution of mutations in RNF43 and TP53, which are acquired during later stages of tumorigenesis. CONCLUSIONS: In an analysis of the heterogeneity of mutations throughout IPMNs, we found that early-stage IPMNs contain multiple independent clones, each with distinct mutations, indicating their polyclonal origin. These findings challenge the model in which pancreatic neoplasms arise from a single clone. Increasing our understanding of the mechanisms of IPMN polyclonality could lead to strategies to identify patients at increased risk for pancreatic cancer.

2 Article IPMNs with co-occurring invasive cancers: neighbours but not always relatives. 2018

Felsenstein, Matthäus / Noë, Michaël / Masica, David L / Hosoda, Waki / Chianchiano, Peter / Fischer, Catherine G / Lionheart, Gemma / Brosens, Lodewijk A A / Pea, Antonio / Yu, Jun / Gemenetzis, Georgios / Groot, Vincent P / Makary, Martin A / He, Jin / Weiss, Matthew J / Cameron, John L / Wolfgang, Christopher L / Hruban, Ralph H / Roberts, Nicholas J / Karchin, Rachel / Goggins, Michael G / Wood, Laura D. ·Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Department of Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany. · Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland, USA. · Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA. · Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Surgery, University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ·Gut · Pubmed #29500184.

ABSTRACT: OBJECTIVE: Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions that can give rise to invasive pancreatic carcinoma. Although approximately 8% of patients with resected pancreatic ductal adenocarcinoma have a co-occurring IPMN, the precise genetic relationship between these two lesions has not been systematically investigated. DESIGN: We analysed all available patients with co-occurring IPMN and invasive intrapancreatic carcinoma over a 10-year period at a single institution. For each patient, we separately isolated DNA from the carcinoma, adjacent IPMN and distant IPMN and performed targeted next generation sequencing of a panel of pancreatic cancer driver genes. We then used the identified mutations to infer the relatedness of the IPMN and co-occurring invasive carcinoma in each patient. RESULTS: We analysed co-occurring IPMN and invasive carcinoma from 61 patients with IPMN/ductal adenocarcinoma as well as 13 patients with IPMN/colloid carcinoma and 7 patients with IPMN/carcinoma of the ampullary region. Of the patients with co-occurring IPMN and ductal adenocarcinoma, 51% were likely related. Surprisingly, 18% of co-occurring IPMN and ductal adenocarcinomas were likely independent, suggesting that the carcinoma arose from an independent precursor. By contrast, all colloid carcinomas were likely related to their associated IPMNs. In addition, these analyses showed striking genetic heterogeneity in IPMNs, even with respect to well-characterised driver genes. CONCLUSION: This study demonstrates a higher prevalence of likely independent co-occurring IPMN and ductal adenocarcinoma than previously appreciated. These findings have important implications for molecular risk stratification of patients with IPMN.

3 Article A novel approach for selecting combination clinical markers of pathology applied to a large retrospective cohort of surgically resected pancreatic cysts. 2017

Masica, David L / Dal Molin, Marco / Wolfgang, Christopher L / Tomita, Tyler / Ostovaneh, Mohammad R / Blackford, Amanda / Moran, Robert A / Law, Joanna K / Barkley, Thomas / Goggins, Michael / Irene Canto, Marcia / Pittman, Meredith / Eshleman, James R / Ali, Syed Z / Fishman, Elliot K / Kamel, Ihab R / Raman, Siva P / Zaheer, Atif / Ahuja, Nita / Makary, Martin A / Weiss, Matthew J / Hirose, Kenzo / Cameron, John L / Rezaee, Neda / He, Jin / Joon Ahn, Young / Wu, Wenchuan / Wang, Yuxuan / Springer, Simeon / Diaz, Luis L / Papadopoulos, Nickolas / Hruban, Ralph H / Kinzler, Kenneth W / Vogelstein, Bert / Karchin, Rachel / Lennon, Anne Marie. ·*Drs Masica and Dal Molin contributed equally as first authors. · Department of Biomedical Engineering and the Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland. · Departments of the Sol Goldman Pancreatic Cancer Research Center. · Departments of Pathology. · Departments of Surgery. · Departments of Oncology. · Departments of Medicine. · Departments of Biostatistics and Bioinformatics. · Departments of the Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland. · Departments of Radiology. · †Drs Lennon and Karchin contributed equally as senior authors amlennon@jhmi.edu karchin@jhu.edu. ·J Am Med Inform Assoc · Pubmed #27330075.

ABSTRACT: OBJECTIVE: Our objective was to develop an approach for selecting combinatorial markers of pathology from diverse clinical data types. We demonstrate this approach on the problem of pancreatic cyst classification. MATERIALS AND METHODS: We analyzed 1026 patients with surgically resected pancreatic cysts, comprising 584 intraductal papillary mucinous neoplasms, 332 serous cystadenomas, 78 mucinous cystic neoplasms, and 42 solid-pseudopapillary neoplasms. To derive optimal markers for cyst classification from the preoperative clinical and radiological data, we developed a statistical approach for combining any number of categorical, dichotomous, or continuous-valued clinical parameters into individual predictors of pathology. The approach is unbiased and statistically rigorous. Millions of feature combinations were tested using 10-fold cross-validation, and the most informative features were validated in an independent cohort of 130 patients with surgically resected pancreatic cysts. RESULTS: We identified combinatorial clinical markers that classified serous cystadenomas with 95% sensitivity and 83% specificity; solid-pseudopapillary neoplasms with 89% sensitivity and 86% specificity; mucinous cystic neoplasms with 91% sensitivity and 83% specificity; and intraductal papillary mucinous neoplasms with 94% sensitivity and 90% specificity. No individual features were as accurate as the combination markers. We further validated these combinatorial markers on an independent cohort of 130 pancreatic cysts, and achieved high and well-balanced accuracies. Overall sensitivity and specificity for identifying patients requiring surgical resection was 84% and 81%, respectively. CONCLUSIONS: Our approach identified combinatorial markers for pancreatic cyst classification that had improved performance relative to the individual features they comprise. In principle, this approach can be applied to any clinical dataset comprising dichotomous, categorical, and continuous-valued parameters.