Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
PLoS One. 2011;6(7):e22250. doi: 10.1371/journal.pone.0022250. Epub 2011 Jul 22.
Comprehensive identification of the acquired mutations that cause common cancers will require genomic analyses of large sets of tumor samples. Typically, the tissue material available from tumor specimens is limited, which creates a demand for accurate template amplification. We therefore evaluated whether phi29-mediated whole genome amplification introduces false positive structural mutations by massive mate-pair sequencing of a normal human genome before and after such amplification. Multiple displacement amplification led to a decrease in clone coverage and an increase by two orders of magnitude in the prevalence of inversions, but did not increase the prevalence of translocations. While multiple strand displacement amplification may find uses in translocation analyses, it is likely that alternative amplification strategies need to be developed to meet the demands of cancer genomics.
全面鉴定导致常见癌症的获得性突变需要对大量肿瘤样本进行基因组分析。通常，从肿瘤标本中获得的组织材料是有限的，这就需要准确的模板扩增。因此，我们通过在大规模 mate-pair 测序前后对正常人类基因组进行 phi29 介导的全基因组扩增，评估了这种扩增是否会引入假阳性结构突变。多重置换扩增导致克隆覆盖率降低，倒位的流行度增加两个数量级，但并未增加易位的流行度。虽然多重链置换扩增可能在易位分析中具有用途，但可能需要开发替代扩增策略来满足癌症基因组学的需求。
