Identification of germline genomic copy number variation in familial pancreatic cancer

被引：23

作者：

Al-Sukhni, Wigdan ^{[2
,10
]}

Joe, Sarah ^{[10
]}

Lionel, Anath C. ^{[3
,4
]}

Zwingerman, Nora ^{[10
]}

Zogopoulos, George ^{[2
,10
]}

Marshall, Christian R. ^{[3
]}

Borgida, Ayelet ^{[10
]}

Holter, Spring ^{[10
]}

Gropper, Aaron ^{[10
]}

Moore, Sara ^{[10
]}

Bondy, Melissa ^{[5
]}

Klein, Alison P. ^{[6
]}

Petersen, Gloria M. ^{[7
]}

Rabe, Kari G. ^{[7
]}

Schwartz, Ann G. ^{[8
]}

Syngal, Sapna ^{[9
]}

Scherer, Stephen W. ^{[3
,4
]}

Gallinger, Steven ^{[1
,2
,10
]}

机构：

[1] Toronto Gen Hosp, Toronto, ON M5G 2C4, Canada

[2] Univ Torontom, Div Gen Surg, Dept Surg, Toronto, ON, Canada

[3] Hosp Sick Children, Ctr Appl Genom, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada

[4] Univ Toronto, Dept Mol Genet, McLaughlin Ctr, Toronto, ON, Canada

[5] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[6] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sol Goldman Pancreat Res Ctr, Baltimore, MD USA

[7] Mayo Clin, Coll Med, Rochester, MN USA

[8] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA

[9] Dana Farber Canc Inst, Boston, MA 02115 USA

[10] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

来源：

HUMAN GENETICS | 2012年 / 131卷 / 09期

关键词：

COLORECTAL-CANCER; RISK; GENE; VARIANTS; DELETIONS; PROSTATE; ONSET; ASSOCIATION; CNV;

D O I：

10.1007/s00439-012-1183-1

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1481 / 1494

页数：14

共 52 条

[51] Germline Copy Number Variations in BRCA1-Associated Ovarian Cancer Patients [J].

Yoshihara, Kosuke ;

Tajima, Atsushi ;

Adachi, Sosuke ;

Quan, Jinhua ;

Sekine, Masayuki ;

Kase, Hiroaki ;

Yahata, Tetsuro ;

Inoue, Ituro ;

Tanaka, Kenichi .

GENES CHROMOSOMES & CANCER, 2011, 50 (03) :167-177

[52] Development of bioinformatics resources for display and analysis of copy number and other structural variants in the human genome [J].

Zhang, J. ;

Feuk, L. ;

Duggan, G. E. ;

Khaja, R. ;

Scherer, S. W. .

CYTOGENETIC AND GENOME RESEARCH, 2006, 115 (3-4) :205-214

← 1 2 3 4 5 6 →