Ha Kyungsik, Kim Hong-Gee, Lee Hwajin
Biomedical Knowledge Engineering Laboratory, Seoul National University, Seoul, 151-742 South Korea.
Interdisciplinary Program of Medical Informatics, College of Medicine, Seoul National University, Seoul, 110-799 South Korea.
NPJ Genom Med. 2017 Apr 3;2:9. doi: 10.1038/s41525-017-0010-y. eCollection 2017.
Somatic mutation rates in cancer differ across the genome in a cancer cell-type specific manner. Although key factors that contribute to the differences were identified, the major cancer progression stage when these factors associate with the mutation variance remained poorly investigated. Here, we analyzed whole-genome sequencing data of pre-cancerous and matching cancer tissues from 173 individuals and 423 normal tissue chromatin features to determine the critical stage of these features contributing to shaping the somatic mutation landscape. Our data showed that the establishment of somatic mutation landscape inferred by chromatin features occur early in the process of cancer progression, and gastric acid reflux environmental exposure-mediated epigenetic changes, represented as gastric metaplasia, at early stage can dramatically impact the somatic mutation landscape. We suggest a possible crucial role of chromatin features during the mutation landscape establishment at early stage of progression in a cancer-type specific manner.
癌症中的体细胞突变率在全基因组中因癌细胞类型而异。尽管已确定了导致这些差异的关键因素，但这些因素与突变差异相关的主要癌症进展阶段仍未得到充分研究。在这里，我们分析了173名个体的癌前和匹配癌组织的全基因组测序数据以及423个正常组织染色质特征，以确定这些特征促成塑造体细胞突变格局的关键阶段。我们的数据表明，由染色质特征推断的体细胞突变格局的建立发生在癌症进展过程的早期，而早期胃酸反流环境暴露介导的表观遗传变化（表现为胃化生）可显著影响体细胞突变格局。我们认为染色质特征在癌症进展早期以癌症类型特异性方式建立突变格局过程中可能起关键作用。
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