title: Comprehensive genomic analysis of a BRCA2 deficient human pancreatic cancer.
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.
authors.affiliation: Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Barber
authors.forename: Juan M
authors.initials: JM
authors.lastname: Rosa Rosa
authors.forename: Iwanka
authors.initials: I
authors.lastname: Kozarewa
authors.forename: Kerry
authors.initials: K
authors.lastname: Fenwick
authors.forename: Ioannis
authors.initials: I
authors.lastname: Assiotis
authors.forename: Costas
authors.initials: C
authors.lastname: Mitsopoulos
authors.forename: David
authors.initials: D
authors.lastname: Sims
authors.forename: Jarle
authors.initials: J
authors.lastname: Hakas
authors.forename: Marketa
authors.initials: M
authors.lastname: Zvelebil
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lord
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D024682:BRCA2 Protein / Q000172:deficiency / Q000235:genetics*; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D055028:Comparative Genomic Hybridization; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D024682:BRCA2 Protein