comprehensive genomic analysis of a brca2 deficient human pancreatic cancer全面的基因组分析人类胰腺癌brca2不足.pdf

Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer . . Louise J. Barber , Juan M. Rosa Rosa , Iwanka Kozarewa, Kerry Fenwick, Ioannis Assiotis, Costas Mitsopoulos, David Sims, Jarle Hakas, Marketa Zvelebil, Christopher J. Lord*, Alan Ashworth* Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom Abstract 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. Citation: Barber LJ, Rosa Rosa JM, Kozarewa I, Fenwick K, Assiotis I, et al. (2011) Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer. PLoS ONE 6(7): e21639. doi:10.1371/journal.pone.0021639 Editor: Robert Oshima, Sanford-Burnham Medical Research Institute, United States of America Received March 17, 2011; Accepted June 3, 2011; Published July 5, 2011 Copyright: 2011 Barber et al. This is an open-