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
2376 - Patient Reported Outcomes (PRO) in patients (pts) with HER2- advanced breast cancer (ABC) and a germline BRCA1/2 mutation (gBRCAm) receiving talazoparib (TALA) vs physician’s choice chemotherapy (PCT) in the EMBRACA trial: A focus on subgroups with/ without visceral disease
Presenter: Johannes Ettl
Session: Poster Display session 2
Resources:
Abstract
4874 - Complete Responses in Patients With 2nd-Line or Greater Metastatic Triple-Negative Breast Cancer (TNBC) Following First-in-Human Immunotherapy Combining NK and T Cell Activation with Off-the-Shelf High-Affinity CD16 NK Cell Line (haNK)
Presenter: Chaitali Nangia
Session: Poster Display session 2
Resources:
Abstract
4362 - Reproducibility and concordance of 4 clinically developed programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays in triple-negative breast cancer (TNBC)
Presenter: Aurelia Noske
Session: Poster Display session 2
Resources:
Abstract
4528 - Systemic Therapy in 2nd-Line Metastatic Triple Negative Breast Cancer (mTNBC): A Systematic Literature Review (SLR) and Meta-Analysis (MA) of Efficacy
Presenter: Peter Kaufman
Session: Poster Display session 2
Resources:
Abstract
4112 - Cisplatin given at three divided doses for three consecutive days in metastatic breast cancer: an alternative schedule for one full dose with comparable efficacy but less CINV and hypomagnesaemia
Presenter: Yang Chen
Session: Poster Display session 2
Resources:
Abstract
5699 - Patterns and predictors of first-line (1L) taxane use in US patients with metastatic triple-negative breast cancer (mTNBC)
Presenter: Joyce O’Shaughnessy
Session: Poster Display session 2
Resources:
Abstract
1931 - Maintenance Chemotherapy is effective in Patients with Metastatic Triple Negative Breast Cancer After First-line Platinum-based Chemotherapy
Presenter: Jian Zhang
Session: Poster Display session 2
Resources:
Abstract
4696 - Using the Patient-Reported Outcomes Measurement Information System (PROMIS) to investigate symptom burden enrichment in Stage IV patients at an academic center
Presenter: Madeline Matthys
Session: Poster Display session 2
Resources:
Abstract
4582 - Measures of functional status in adults aged ≥70 years with advanced breast cancer (ABC) receiving palbociclib (PAL) combination therapy in POLARIS
Presenter: Meghan Karuturi
Session: Poster Display session 2
Resources:
Abstract
3565 - Real-World 1-Year Survival Analysis of Patients with Metastatic Breast Cancer with Liver or Lung Metastasis Treated with Eribulin, Gemcitabine or Capecitabine
Presenter: Shayma Kazmi
Session: Poster Display session 2
Resources:
Abstract