Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom.
PLoS One. 2011;6(7):e21639. doi: 10.1371/journal.pone.0021639. Epub 2011 Jul 5.
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.
Capan-1 是一种经过充分表征的 BRCA2 缺陷型人细胞系，源自胰腺腺癌的肝转移。在这里，我们报告了对 Capan-1 中结构变异的全基因组评估，以及对单核苷酸变异和小插入/缺失的高深度外显子组特征分析。为了在没有匹配的正常细胞系的情况下识别潜在的体细胞和肿瘤相关变异，我们设计了一种基于 HapMap 样本分析的新方法。我们证明 Capan-1 具有迄今为止测序的最具重排的基因组之一。此外，与其他基因组相比，短序列重复中的小插入和缺失更频繁地被检测到。我们还鉴定了一些新的突变，这些突变可能代表促进肿瘤进展的遗传变化。这些数据为了解 BRCA2 功能丧失的基因组影响提供了线索。
