Futreal P A, Kasprzyk A, Birney E, Mullikin J C, Wooster R, Stratton M R
Cancer Genome Project, Sanger Centre, Cambridge, UK.
Nature. 2001 Feb 15;409(6822):850-2. doi: 10.1038/35057046.
Identification of the genes that cause oncogenesis is a central aim of cancer research. We searched the proteins predicted from the draft human genome sequence for paralogues of known tumour suppressor genes, but no novel genes were identified. We then assessed whether it was possible to search directly for oncogenic sequence changes in cancer cells by comparing cancer genome sequences against the draft genome. Apparently chimaeric transcripts (from oncogenic fusion genes generated by chromosomal translocations, the ends of which mapped to different genomic locations) were detected to the same degree in both normal and neoplastic tissues, indicating a significant level of false positives. Our experiment underscores the limited amount and variable quality of DNA sequence from cancer cells that is currently available.
确定导致肿瘤发生的基因是癌症研究的核心目标。我们在人类基因组序列草图预测的蛋白质中搜索已知肿瘤抑制基因的旁系同源物,但未发现新基因。然后,我们评估了通过将癌症基因组序列与基因组草图进行比较,是否有可能直接在癌细胞中搜索致癌序列变化。在正常组织和肿瘤组织中均以相同程度检测到明显的嵌合转录本(来自由染色体易位产生的致癌融合基因,其末端映射到不同的基因组位置),这表明假阳性水平很高。我们的实验强调了目前可用的癌细胞DNA序列数量有限且质量参差不齐。