Distinct Mutational Patterns of Infection and Non-Infection-Related Bile Duct Cancers Revealed by Exome Sequencing (Genome variation profiling by SNP array)

From GEO summary: The impact of different carcinogenic exposures on the specific patterns of somatic mutations in human tumors remains unclear. To clarify this issue, we profiled 209 cholangiocarcinomas (CCAs) from Asia and Europe, including 108 cases caused by liver fluke Opisthorchis viverrini (OV)-infection and 101 cases due to non-OV etiologies. Whole-exome (N = 15) and prevalence screening (N = 194) revealed recurrent somatic mutations in BAP1 and ARID1A, neither of which has been previously reported to be mutated in CCA. Comparisons between intrahepatic OV and non-OV CCAs demonstrated statistically significant different mutation patterns: BAP1 and IDH1/2 were more frequently mutated in non-OV CCAs, while TP53 displayed the reciprocal pattern. Functional studies demonstrated tumor suppressive roles of BAP1 and ARID1A, establishing the role of chromatin modulators in CCA pathogenesis. These findings indicate that different causative etiologies may induce distinct somatic alterations even within the same tumor type.

根据 GEO 摘要：不同致癌暴露对人类肿瘤中特定体细胞突变模式的影响尚不明确。为阐明这一问题，我们对来自亚洲和欧洲的 209 例胆管癌（CCAs）进行了基因表达分析，其中包括由肝吸虫 Opisthorchis viverrini（OV）感染引起的 108 例病例和由非 OV 原因引起的 101 例病例。全外显子组测序（N = 15）和普遍筛查（N = 194）揭示了 BAP1 和 ARID1A 中反复出现的体细胞突变，这两种突变此前均未报道出现在 CCA 中。肝内 OV 和非 OV CCA 之间的比较显示了统计学上显著的突变模式差异：非 OV CCA 中 BAP1 和 IDH1/2 突变的频率更高，而 TP53 则表现出相反的模式。功能研究证实了 BAP1 和 ARID1A 的肿瘤抑制功能，确立了组蛋白修饰因子在 CCA 发病机制中的作用。这些发现表明，不同的致病原因可能导致同一种肿瘤类型中不同的体细胞改变。