Abstract 3881
Background
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers without effective therapy. To explore therapeutic options, the mutational profile of ESCC tumors has to be elucidated to understand the molecular mechanism of its development and explore targetable mutations. In this study, we aim to elucidate the mutational profile of ESCC patients.
Methods
Capture-based targeted sequencing was performed on tissue samples surgically-removed from 29 early-stage ESCC patients using a 520-gene panel to comprehensively profile the genomic alterations in ESCC. Tumor mutation burden was also estimated for all the samples.
Results
A total of 421 mutations in 39 genes were detected in all the patients, revealing a mutation detection rate of 100%. The mutation types detected in the cohort included 55% single nucleotide variations, 35% copy number amplification and the remaining 10% were small insertion-deletions and large deletions. Except for 1 patient, all of the patients were TP53 mutant. Copy number amplifications (CNA) in CCND1, FGF3, FGF4 and FGF19 were found in 41% (12/29) of the patients, respectively, with all CNA in 4 genes occurring concurrently in all patients. Interestingly, mutations in NFκB1A, previously unreported in ESCC, were detected in 21% (6/29) of the patients. Further analysis reveals mutations in genes involved in pathways including cell cycle, chromatin modification, Notch and JAK-STAT signaling, suggesting that these may be the most critical pathways involved in the development and progression of ESCC. No actionable mutations in receptor tyrosine kinases were detected in our cohort. Instead, potential therapeutic target analysis identified CDKN2A and PIK3CA, with mutation detection rate of 20.7% and 13.8%, respectively, as candidates for targeted therapy. In addition, the median TMB of the cohort was 5.6 mutations/Mb, ranging from 0.8 to 42.9 mutations/Mb.
Conclusions
Our study reveals the comprehensive mutation profile of ESCC tumors, shedding light on potential molecular mechanisms associated with its development and possible therapeutic options for ESCC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2078 - Comprehensive genomic profiling and clinical outcomes in patients (pts) with fibroblast growth factor receptor rearrangement-positive (FGFR2+) cholangiocarcinoma (CCA) treated with pemigatinib in the fight-202 trial
Presenter: Antoine Hollebecque
Session: Poster Display session 2
Resources:
Abstract
3879 - Efficacy of derazantinib (DZB) in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) expressing FGFR2-fusion or FGFR2 mutations/amplifications
Presenter: Michele Droz Dit Busset
Session: Poster Display session 2
Resources:
Abstract
4679 - It’s Not Only About Weight Loss: Tackling Pancreatic Cancer-Associated Cachexia
Presenter: Ana Leonor Matos
Session: Poster Display session 2
Resources:
Abstract
2276 - Frequency and clinicopathological characteristics of biliary tract carcinomas harboring the FGFR2-fusion gene: a prospective observational study (PRELUDE study)
Presenter: Masafumi Ikeda
Session: Poster Display session 2
Resources:
Abstract
2773 - Post-hoc analyses of a subgroup of patients with advanced biliary tract cancer (BTC) who crossed over to treatment with etoposide toniribate (EDO-S7.1) in a randomized Phase II study
Presenter: Ulrich-Frank Pape
Session: Poster Display session 2
Resources:
Abstract
4479 - Capecitabine +Best supportive care (BSC) or Erlotinib +BSC has Overall survival (OS) benefit over BSC alone in unresectable/metastatic Gall bladder cancer(GBC) patients with ECOG PS-III. Results from a phase II Randomised controlled trial (RCT)
Presenter: Babita Kataria
Session: Poster Display session 2
Resources:
Abstract
4843 - FGFR2 fusions and its effect of patient (pt) outcomes in intrahepatic cholangiocarcinoma (iCCA)
Presenter: Daniel Almquist
Session: Poster Display session 2
Resources:
Abstract
2324 - The Clinical Outcomes of Systemic Chemotherapy in Patients with Unresectable or Metastatic Combined Hepatocellular-cholangiocarcinoma (HCC-CCA): Retrospective Study of 120 Patients
Presenter: Eojin Kim
Session: Poster Display session 2
Resources:
Abstract
3678 - High PD-L1 expression is associated with treatment response to pembrolizumab in patients with advanced biliary tract cancer.
Presenter: Gilhyang Kim
Session: Poster Display session 2
Resources:
Abstract
3901 - Genomic profiling in Chinese biliary tract cancer patients with PI3K/AKT/mTOR pathway and RAS gene mutations
Presenter: Jingyu Cao
Session: Poster Display session 2
Resources:
Abstract