Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer

被引：16

作者：

Barber, Louise J. ^{[1
]}

Rosa, Juan M. Rosa ^{[1
]}

Kozarewa, Iwanka ^{[1
]}

Fenwick, Kerry ^{[1
]}

Assiotis, Ioannis ^{[1
]}

Mitsopoulos, Costas ^{[1
]}

Sims, David ^{[1
]}

Hakas, Jarle ^{[1
]}

Zvelebil, Marketa ^{[1
]}

Lord, Christopher J. ^{[1
]}

Ashworth, Alan ^{[1
]}

机构：

[1] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

来源：

PLOS ONE | 2011年 / 6卷 / 07期

关键词：

HOMOLOGY-DIRECTED REPAIR; COLORECTAL-CANCER; HUMAN BREAST; CELL-LINES; GENE; MUTATIONS; PROTEIN; DCC; DNA; SEQUENCE;

D O I：

10.1371/journal.pone.0021639

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Capan-1 is a well-characterised BRCA2-deficient human cell line isolated from a liver metastasis of a pancreatic adenocarcinoma. Here we report a genome-wide assessment of structural variations and high-depth exome characterization of single nucleotide variants and small insertion/deletions in Capan-1. To identify potential somatic and tumour-associated variations in the absence of a matched-normal cell line, we devised a novel method based on the analysis of HapMap samples. We demonstrate that Capan-1 has one of the most rearranged genomes sequenced to date. Furthermore, small insertions and deletions are detected more frequently in the context of short sequence repeats than in other genomes. We also identify a number of novel mutations that may represent genetic changes that have contributed to tumour progression. These data provide insight into the genomic effects of loss of BRCA2 function.

引用

页数：12

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