American Association for Cancer Research
cd-23-0902_supplementary_table_s2_suppst2.xlsx (37.76 kB)

Supplementary Table S2 from Pan-Cancer Comparative and Integrative Analyses of Driver Alterations Using Japanese and International Genomic Databases

Download (37.76 kB)
posted on 2024-05-01, 07:41 authored by Sara Horie, Yuki Saito, Yasunori Kogure, Kota Mizuno, Yuta Ito, Mariko Tabata, Takanori Kanai, Koichi Murakami, Junji Koya, Keisuke Kataoka

Targeted genes in each gene panel


Japan Society for the Promotion of Science (JSPS)

Takeda Science Foundation (TSF)

Uehara Memorial Foundation (UMF)

Japan Agency for Medical Research and Development (AMED)

Japan Science and Technology Agency Moonshot R&D Program



Using 48,627 samples from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), we present a pan-cancer landscape of driver alterations and their clinical actionability in Japanese patients. Comparison with White patients in Genomics Evidence Neoplasia Information Exchange (GENIE) demonstrates high TP53 mutation frequencies in Asian patients across multiple cancer types. Integration of C-CAT, GENIE, and The Cancer Genome Atlas data reveals many cooccurring and mutually exclusive relationships between driver mutations. At pathway level, mutations in epigenetic regulators frequently cooccur with PI3K pathway molecules. Furthermore, we found significant cooccurring mutations within the epigenetic pathway. Accumulation of mutations in epigenetic regulators causes increased proliferation-related transcriptomic signatures. Loss-of-function of many epigenetic drivers inhibits cell proliferation in their wild-type cell lines, but this effect is attenuated in those harboring mutations of not only the same but also different epigenetic drivers. Our analyses dissect various genetic properties and provide valuable resources for precision medicine in cancer. We present a genetic landscape of 26 principal cancer types/subtypes, including Asian-prevalent ones, in Japanese patients. Multicohort data integration unveils numerous cooccurring and exclusive relationships between driver mutations, identifying cooccurrence of multiple mutations in epigenetic regulators, which coordinately cause transcriptional and phenotypic changes. These findings provide insights into epigenetic regulator–driven oncogenesis.This article is featured in Selected Articles from This Issue, p. 695