Epigenetic landscape influences the liver cancer genome architecture.
Epigenetic landscape influences the liver cancer genome architecture.
复制标题
DOI：
10.1038/s41467-018-03999-y
复制
发表时间：
2018-04-24
影响因子：
16.6
通讯作者：
Shibata T
中科院分区：
文献类型：
--
作者：
Hama N;Totoki Y;Miura F;Tatsuno K;Saito-Adachi M;Nakamura H;Arai Y;Hosoda F;Urushidate T;Ohashi S;Mukai W;Hiraoka N;Aburatani H;Ito T;Shibata T
不同类型的遗传改变如核苷酸替换、结构重排和病毒基因组整合以及表观遗传改变的积累有助于致癌。在这里，我们报告了373例肝癌的表观遗传特征和全基因组亚硫酸氢盐，全基因组鸟枪，长读和病毒捕获测序的遗传畸变之间的相关性。体细胞置换和重排断点富集在具有非活性染色质标记的肿瘤特异性低甲基化区域和癌症基因组中活跃转录的高度甲基化区域中。个体突变特征依赖于染色质状态，特别是，具有较高转录链偏好的特征发生在活跃染色质区域内。作为活性染色质区域中整合的负选择的结果，经常在癌细胞的非活性染色质区域中检测到B型肝炎病毒（HBV）整合位点。观察到整合的HBV基因组的超高结构不稳定性和保留的非甲基化。我们的结论是，癌前和体细胞表观遗传特征有助于癌症基因组结构。基因组畸变有助于癌症的发展;然而，它们之间的相互依赖性仍然知之甚少。在这里，作者分析了肝癌样本，以发现表观遗传特征和遗传畸变之间的相关性，包括体细胞置换，突变特征和HBV整合位点。
The accumulations of different types of genetic alterations such as nucleotide substitutions, structural rearrangements and viral genome integrations and epigenetic alterations contribute to carcinogenesis. Here, we report correlation between the occurrence of epigenetic features and genetic aberrations by whole-genome bisulfite, whole-genome shotgun, long-read, and virus capture sequencing of 373 liver cancers. Somatic substitutions and rearrangement breakpoints are enriched in tumor-specific hypo-methylated regions with inactive chromatin marks and actively transcribed highly methylated regions in the cancer genome. Individual mutation signatures depend on chromatin status, especially, signatures with a higher transcriptional strand bias occur within active chromatic areas. Hepatitis B virus (HBV) integration sites are frequently detected within inactive chromatin regions in cancer cells, as a consequence of negative selection for integrations in active chromatin regions. Ultra-high structural instability and preserved unmethylation of integrated HBV genomes are observed. We conclude that both precancerous and somatic epigenetic features contribute to the cancer genome architecture. Genomic aberrations contribute to the development of cancer; however, their interdependence remains poorly understood. Here the authors analyze liver cancer samples to find correlation between epigenetic features and genetic aberrations including somatic substitutions, mutation signatures, and HBV integration sites.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Sabarinathan, Radhakrishnan;Mularoni, Loris;Lopez-Bigas, Nuria
通讯作者：
Lopez-Bigas, Nuria
影响因子：
7
作者：
Jiang, Zhaoshi;Jhunjhunwala, Suchit;Zhang, Zemin
通讯作者：
Zhang, Zemin
DOI：
10.1073/pnas.82.1.208
发表时间：
1985-01-01
影响因子：
11.1
作者：
MIZUSAWA, H;TAIRA, M;KOIKE, K
通讯作者：
KOIKE, K
影响因子：
64.5
作者：
KOSHY, R;KOCH, S;HOFSCHNEIDER, PH
通讯作者：
HOFSCHNEIDER, PH