Lin Jiannan, Shi Tieliu
The Center for Bioinformatics and Computational Biology, Shanghai Key Laboratory of Regulatory Biology, The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
Oncotarget. 2017 Jul 11;8(28):45154-45163. doi: 10.18632/oncotarget.13293.
Mutational processes for A→G mutations in tumors are not well understood. To uncover the mutational mechanisms, we analyzed molecular profiles of more than 9,000 tumor samples from The Cancer Genome Atlas (TCGA). The present study found that error-prone DNA polymerases were involved in stomach tumors with high fraction of A→G mutations. High levels of apoptosis in kidney cancers and high levels of energy metabolism in thyroid cancers increased A→G mutation rate, which was associated with high oxidative stress. We also found that the frequencies of RAS gene mutations were increased in thyroid cancers with high level of energy metabolism because of high-frequency A→G mutations.
肿瘤中A→G突变的突变过程尚未完全了解。为了揭示突变机制，我们分析了来自癌症基因组图谱（TCGA）的9000多个肿瘤样本的分子特征。本研究发现，易出错的DNA聚合酶参与了具有高比例A→G突变的胃肿瘤。肾癌中的高凋亡水平和甲状腺癌中的高能量代谢水平增加了A→G突变率，这与高氧化应激有关。我们还发现，由于高频A→G突变，能量代谢水平高的甲状腺癌中RAS基因突变的频率增加。
