Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate.
Akhilesh PandeyEric W StawiskiSteffen DurinckHarsha GowdaLeonard D GoldsteinMustafa A BarbhuiyaMarkus S SchröderSreelakshmi K SreenivasamurthySun-Whe KimSameer PhalkeKushal SuryamohanKayla LeePapia ChakrabortyVasumathi KodeXiaoshan ShiAditi ChatterjeeKeshava DattaAafaque A KhanTejaswini SubbannayyaJing WangSubhra ChaudhuriSanjiv GuptaBraj Raj ShrivastavBijay S JaiswalSatish S PoojaryShushruta BhuniaPatricia GarciaCarolina BizamaLorena RosaWooil KwonHyeong Seok KimYoungmin HanThakur Deen YadavVedam L RamprasadAmitabha ChaudhuriZora ModrusanJuan Carlos RoaPramod Kumar TiwariJin-Young JangSomasekar SeshagiriPublished in: Nature communications (2020)
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.