日本国立癌症中心研究所Tatsuhiro Shibata团队近期取得重要工作进展，他们对胃癌的多血统基因组和转录组进行了分析。相关研究成果2023年3月13日在线发表于《自然—遗传学》杂志上。
据介绍，癌症是世界上最常见的恶性肿瘤之一，具有地理、流行病学和组织学异质性的特点。
研究人员报告了一个涉及1335个案例的驱动胃癌发生的广泛、多血统概况。共鉴定出77个显著突变基因（SMG），包括ARHGAP5和TRIM49C。研究人员还确定了亚型特异性驱动因素，包括PIGR和SOX9，它们在疾病的弥漫性亚型中富集。SMG也因Epstein–Barr（EB）病毒感染状况和血统而异。非蛋白质截断CDH1突变，其特征是框内剪接改变，靶向局部细胞外结构域，并且独特地发生在散发性弥漫型病例中。在具有东亚血统的癌症患者中，这一数据表明，饮酒或代谢与RHOA突变的发展之间存在联系。
此外，研究人员还发现了在免疫逃避中具有潜在作用的突变。
总的来说，这些数据为不同亚型和起源的癌症分子概况提供了全面的见解。
附：英文原文
Title: Multiancestry genomic and transcriptomic analysis of gastric cancer
Author: Totoki, Yasushi, Saito-Adachi, Mihoko, Shiraishi, Yuichi, Komura, Daisuke, Nakamura, Hiromi, Suzuki, Akihiro, Tatsuno, Kenji, Rokutan, Hirofumi, Hama, Natsuko, Yamamoto, Shogo, Ono, Hanako, Arai, Yasuhito, Hosoda, Fumie, Katoh, Hiroto, Chiba, Kenichi, Iida, Naoko, Nagae, Genta, Ueda, Hiroki, Shihang, Chen, Sekine, Shigeki, Abe, Hiroyuki, Nomura, Sachiyo, Matsuura, Tetsuya, Sakai, Eiji, Ohshima, Takashi, Rino, Yasushi, Yeoh, Khay Guan, So, Jimmy, Sanghvi, Kaushal, Soong, Richie, Fukagawa, Akihiko, Yachida, Shinichi, Kato, Mamoru, Seto, Yasuyuki, Ushiku, Tetsuo, Nakajima, Atsushi, Katai, Hitoshi, Tan, Patrick, Ishikawa, Shumpei, Aburatani, Hiroyuki, Shibata, Tatsuhiro
Issue&Volume: 2023-03-13
Abstract: Gastric cancer is among the most common malignancies worldwide, characterized by geographical, epidemiological and histological heterogeneity. Here, we report an extensive, multiancestral landscape of driver events in gastric cancer, involving 1,335 cases. Seventy-seven significantly mutated genes (SMGs) were identified, including ARHGAP5 and TRIM49C. We also identified subtype-specific drivers, including PIGR and SOX9, which were enriched in the diffuse subtype of the disease. SMGs also varied according to Epstein–Barr virus infection status and ancestry. Non-protein-truncating CDH1 mutations, which are characterized by in-frame splicing alterations, targeted localized extracellular domains and uniquely occurred in sporadic diffuse-type cases. In patients with gastric cancer with East Asian ancestry, our data suggested a link between alcohol consumption or metabolism and the development of RHOA mutations. Moreover, mutations with potential roles in immune evasion were identified. Overall, these data provide comprehensive insights into the molecular landscape of gastric cancer across various subtypes and ancestries.
DOI: 10.1038/s41588-023-01333-x
Source: https://www.nature.com/articles/s41588-023-01333-x
Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
