PLoS ONE (Jan 2011)

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

DOI
https://doi.org/10.1371/journal.pone.0021639
Journal volume & issue
Vol. 6, no. 7
p. e21639

Abstract

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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.