Zhidkov Ilia, Livneh Erez A, Rubin Eitan, Mishmar Dan
Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Genome Res. 2009 Apr;19(4):576-80. doi: 10.1101/gr.086462.108. Epub 2009 Feb 10.
Multiple human mutational landscapes of normal and cancer conditions are currently available. However, while the unique mutational patterns of tumors have been extensively studied, little attention has been paid to similarities between malignant and normal conditions. Here we compared the pattern of mutations in the mitochondrial genomes (mtDNAs) of cancer (98 sequences) and natural populations (2400 sequences). De novo mtDNA mutations in cancer preferentially colocalized with ancient variants in human phylogeny. A significant portion of the cancer mutations was organized in recurrent combinations (COMs), reaching a length of seven mutations, which also colocalized with ancient variants. Thus, by analyzing similarities rather than differences in patterns of mtDNA mutations in tumor and human evolution, we discovered evidence for similar selective constraints, suggesting a functional potential for these mutations.
目前已有多种正常和癌症状态下的人类突变图谱。然而，尽管肿瘤独特的突变模式已得到广泛研究，但对恶性和正常状态之间的相似性却很少关注。在这里，我们比较了癌症（98个序列）和自然群体（2400个序列）线粒体基因组（mtDNA）中的突变模式。癌症中从头发生的mtDNA突变优先与人类系统发育中的古老变体共定位。相当一部分癌症突变以反复出现的组合（COMs）形式组织起来，长度达到七个突变，这些组合也与古老变体共定位。因此，通过分析肿瘤和人类进化中mtDNA突变模式的相似性而非差异，我们发现了类似选择限制的证据，这表明这些突变具有功能潜力。
