Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32839463.
- Also identified by DOI 10.1038/s41467-020-17880-4 and PMC identifier 7445288.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Gallbladder cancer (GBC) is an aggressive gastrointestinal malignancy with no approved targeted therapy. Here, we analyze exomes (n = 160), transcriptomes (n = 115), and low pass whole genomes (n = 146) from 167 gallbladder cancers (GBCs) from patients in Korea, India and Chile. In addition, we also sequence samples from 39 GBC high-risk patients and detect evidence of early cancer-related genomic lesions. Among the several significantly mutated genes not previously linked to GBC are ETS domain genes ELF3 and EHF, CTNNB1, APC, NSD1, KAT8, STK11 and NFE2L2. A majority of ELF3 alterations are frame-shift mutations that result in several cancer-specific neoantigens that activate T-cells indicating that they are cancer vaccine candidates. In addition, we identify recurrent alterations in KEAP1/NFE2L2 and WNT pathway in GBC. Taken together, these define multiple targetable therapeutic interventions opportunities for GBC treatment and management.
Medical subject headings
- DNA-Binding Proteins
- Frameshift Mutation
- Gallbladder Neoplasms
- Genetic Predisposition to Disease
- Proto-Oncogene Proteins c-ets
- Transcription Factors