Identification of germline genomic copy number variation in familial pancreatic cancer.
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.
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada. wigdan.al.sukhni@utoronto.ca
Wigdan
W
Al-Sukhni
Sarah
S
Joe
Anath C
AC
Lionel
Nora
N
Zwingerman
George
G
Zogopoulos
Christian R
CR
Marshall
Ayelet
A
Borgida
Spring
S
Holter
Aaron
A
Gropper
Sara
S
Moore
Melissa
M
Bondy
Alison P
AP
Klein
Gloria M
GM
Petersen
Kari G
KG
Rabe
Ann G
AG
Schwartz
Sapna
S
Syngal
Stephen W
SW
Scherer
Steven
S
Gallinger
D000230:Adenocarcinoma / Q000235:genetics*; D016022:Case-Control Studies; D018628:Gene Dosage; D005854:Germ Cells; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction