@article{41cf9525a0ca4a43a5d6530d37cfb98e,
title = "Identification of germline genomic copy number variation in familial pancreatic cancer",
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.",
author = "Wigdan Al-Sukhni and Sarah Joe and Lionel, {Anath C.} and Nora Zwingerman and George Zogopoulos and Marshall, {Christian R.} and Ayelet Borgida and Spring Holter and Aaron Gropper and Sara Moore and Melissa Bondy and Klein, {Alison P.} and Petersen, {Gloria M.} and Rabe, {Kari G.} and Schwartz, {Ann G.} and Sapna Syngal and Scherer, {Stephen W.} and Steven Gallinger",
note = "Funding Information: Acknowledgments Sources of funding were from National Institute of Health, Pancreatic Cancer Genetic Epidemiology Consortium (PACGENE) Grant#5R01CA097975-08; Lustgarten Foundation; Princess Margaret Hospital Invest-in-Research Fund; Canadian Institute for Health Research (Graduate Research Award; Vanier Doctoral Award); Canadian Society for Surgical Oncology; American Hepato-Pancreato-Biliary Association; Johnson & Johnson Medical Products/University of Toronto Surgeon Scientist Program Fellowship. We thank the following individuals for their contributions: A. Fiebig, A. Franke and S. Schreiber at POPGEN (University of Kiel, Kiel, Germany) and A. Stewart, R. McPherson and R. Roberts of the University of Ottawa Heart Institute (University of Ottawa, Ottawa, Canada) for generously providing population control micro-array data; D. Merico and D. Pinto (The Centre for Applied Genomics, Toronto, Canada) for assistance with data review; G. Bader (University of Toronto, Toronto, Canada) and S. Narod (Women{\textquoteright}s College Hospital, Toronto, Canada) for review of the manuscript; H. Rothenmund (Samuel Lunenefeld Research Institute, Toronto, Canada) for her help with patient selection for the study; T. Selander of the Biospecimen Repository (Samuel Lunenfeld Research Institute, Toronto, Canada) for DNA extraction and storage. PACGENE coordinators (Mayo Clinic: J. Cogswell, T. Hammer, C. Wong; JHU: D. Echavarria; Karmanos: K. Sargent; MDA: P. Adatto, G. Armstrong; Dana Farber: M. Lenn, M. Perez, C. Ukaegbu).",
year = "2012",
month = sep,
doi = "10.1007/s00439-012-1183-1",
language = "English (US)",
volume = "131",
pages = "1481--1494",
journal = "Human genetics",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "9",
}