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Sequencing 167 gallbladder cancers from Korea, India and Chile uncovered new driver genes, notably ELF3, whose frameshift mutations create tumour-specific fragments that T cells recognise, making it a candidate for a cancer vaccine.
Exomes (n = 160), transcriptomes (n = 115) and low-pass whole genomes (n = 146) from 167 gallbladder cancers from patients in Korea, India and Chile were analysed, together with samples from 39 high-risk patients in whom early cancer-related genomic lesions were detected. Among the significantly mutated genes not previously linked to gallbladder cancer were the ETS domain genes ELF3 and EHF, CTNNB1, APC, NSD1, KAT8, STK11 and NFE2L2.
A majority of ELF3 alterations were frameshift mutations that result in several cancer-specific neoantigens that activate T cells, indicating they are cancer vaccine candidates. Recurrent alterations in KEAP1/NFE2L2 and the Wnt pathway were identified, together defining multiple targetable intervention opportunities.
A three-continent cohort from high-incidence countries, and the origin of the idea that a shared frameshift (ELF3) could be a vaccine target in a cancer with few targets. CTNNB1 and STK11 from this list recur in the MSK data.
Shares CTNNB1, Nature Communications, Wnt / β-catenin, Gallbladder cancer.
Shares CTNNB1, APC, Wnt / β-catenin.
Shares ELF3, Gallbladder cancer.
Shares APC, Wnt / β-catenin.
Shares CTNNB1, APC, Wnt / β-catenin.