Multiancestry genomic and transcriptomic analysis of gastric cancer
Menée à partir de données génomiques et transcriptomiques portant sur 1 335 patients atteints d'un cancer de l'estomac, cette étude identifie les caractéristiques moléculaires des tumeurs gastriques et met en évidence des associations entre des mutations "conductrices", l'ascendance ethnique des patients et des sous-types cliniques de la maladie
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.
Nature Genetics , résumé, 2023