Identification of germline genomic copy number variation in familial pancreatic cancer

Wigdan Al-Sukhni, Sarah Joe, Anath C. Lionel, Nora Zwingerman, George Zogopoulos, Christian R. Marshall, Ayelet Borgida, Spring Holter, Aaron Gropper, Sara Moore, Melissa Bondy, Alison P. Klein, Gloria M. Petersen, Kari G. Rabe, Ann G. Schwartz, Sapna Syngal, Stephen W. Scherer, Steven Gallinger

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1481-1494
Number of pages14
JournalHuman genetics
Issue number9
StatePublished - Sep 2012

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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