Multiancestry genomic and transcriptomic analysis of gastric cancer
Multiancestry genomic and transcriptomic analysis of gastric cancer
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DOI：
10.1038/s41588-023-01333-x
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发表时间：
2023-03
期刊：
影响因子：
30.8
通讯作者：
Y. Totoki;Mihoko Saito-Adachi;Y. Shiraishi;D. Komura;Hiromi Nakamura;Akihiro Suzuki;K. Tatsuno;Hirofumi Rokutan;Natsuko Hama;Shogo Yamamoto;Hanako Ono;Y. Arai;F. Hosoda;H. Katoh;K. Chiba;N. Iida;G. Nagae;Hiroki Ueda;Shihang Chen;S. Sekine;Hiroyuki Abe;S. Nomura;Tetsuya Matsuura;E. Sakai;T. Ohshima;Y. Rino;K. Yeoh;J. So;Kaushal Sanghvi;R. Soong;A. Fukagawa;S. Yachida;Mamoru Kato;Y. Seto;T. Ushiku;A. Nakajima;H. Katai;P. Tan;S. Ishikawa;H. Aburatani;T. Shibata
中科院分区：
文献类型：
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作者：
Y. Totoki;Mihoko Saito-Adachi;Y. Shiraishi;D. Komura;Hiromi Nakamura;Akihiro Suzuki;K. Tatsuno;Hirofumi Rokutan;Natsuko Hama;Shogo Yamamoto;Hanako Ono;Y. Arai;F. Hosoda;H. Katoh;K. Chiba;N. Iida;G. Nagae;Hiroki Ueda;Shihang Chen;S. Sekine;Hiroyuki Abe;S. Nomura;Tetsuya Matsuura;E. Sakai;T. Ohshima;Y. Rino;K. Yeoh;J. So;Kaushal Sanghvi;R. Soong;A. Fukagawa;S. Yachida;Mamoru Kato;Y. Seto;T. Ushiku;A. Nakajima;H. Katai;P. Tan;S. Ishikawa;H. Aburatani;T. Shibata
胃癌是全世界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。在此，我们报告了胃癌驱动事件的广泛、多祖先景观，涉及 1,335 例。鉴定出 77 个显着突变基因 (SMG)，包括 ARHGAP5 和 TRIM49C。我们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丰富。 SMG 还根据 Epstein-Barr 病毒感染状态和血统而变化。非蛋白质截断 CDH1 突变的特点是框内剪接改变，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。在东亚血统的胃癌患者中，我们的数据表明饮酒或新陈代谢与 RHOA 突变的发生之间存在联系。此外，还确定了在免疫逃避中具有潜在作用的突变。总体而言，这些数据提供了对不同亚型和血统的胃癌分子景观的全面见解。
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, includingARHGAP5andTRIM49C. We also identified subtype-specific drivers, includingPIGRandSOX9, which were enriched in the diffuse subtype of the disease. SMGs also varied according to Epstein–Barr virus infection status and ancestry. Non-protein-truncatingCDH1mutations, 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 ofRHOAmutations. 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.