학술논문

Multiancestry genomic and transcriptomic analysis of gastric cancer
Document Type
Article
Source
Nature Genetics; April 2023, Vol. 55 Issue: 4 p581-594, 14p
Subject
Language
ISSN
10614036; 15461718
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 ARHGAP5and TRIM49C. We also identified subtype-specific drivers, including PIGRand 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 CDH1mutations, 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 RHOAmutations. 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.