Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 03722, South Korea.
Sci Rep. 2017 Oct 27;7(1):14204. doi: 10.1038/s41598-017-14543-1.
Accumulation of DNA mutations alters amino acid sequence in the key domains of oncoproteins, leading to cellular malignant transformation. Due to redundancy of the genetic code, the same amino acid alteration can be achieved by multiple distinct genetic mutations, which are considered functionally identical and not actively distinguished in the current cancer genome research. For the first time, we analyzed the distribution of codon level transitions acquired by somatic mutations in human cancers. By analyzing the ~2.5 million nonsynonymous somatic single nucleotide variations (SNVs) found in the COSMIC database, we found 41 recurrent amino acid alterations whose DNA changes are significantly biased toward a specific codon transition. Additional analyses partially identified functional discrepancies between the favored and avoided codon transitions in terms of mutational process, codon usage, alternative splicing, and mRNA stability.
DNA 突变的积累会改变癌蛋白关键结构域中的氨基酸序列，导致细胞恶性转化。由于遗传密码的冗余性，相同的氨基酸改变可以通过多种不同的基因突变来实现，这些基因突变在当前的癌症基因组研究中被认为在功能上是相同的，并且没有被积极区分。我们首次分析了人类癌症中体细胞突变获得的密码子水平转换的分布。通过分析 COSMIC 数据库中发现的约 250 万个非同义体细胞单核苷酸变异 (SNV)，我们发现了 41 个反复出现的氨基酸改变，其 DNA 变化明显偏向于特定的密码子转换。进一步的分析部分确定了有利和不利密码子转换在突变过程、密码子使用、选择性剪接和 mRNA 稳定性方面的功能差异。
