The genetic profiles of esophageal squamous cell carcinoma (ESCC) in Hebei, a northern province of China.

Abstract

e15558 Background: Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. Methods: DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) sections from 29 ESCC samples. A panel of 520 genes was sequenced with NGS to identify genomic alterations at an average sequencing depth of 1000×. Results: In total, 421 genomic alterations were identified. We identified 230 single nucleotide variants (SNVs) and 35 insertions and deletions (indels) , 147 CNAs, 9 deletions and 0 translocations. The most frequently mutated genes were TP53 (97%), NOTCH1 (31%), CDKN2A (21%), NFKBIA (21%). Most frequent CN gains were observed in FGF3/4/19/CCND1(41%) which were co-occurrence in cBioPortal.By performing targeted NGS in 29 ESCC samples, we found a median TMB of 5.6/Mb (range: 0.8 to 42.9/Mb).TMB-high was located according to TMB > = 10, where 17.2% of the samples were TMB-H.C·G > T·A transversions were the most common mutations, followed by G·C > A·T transitions,The patients with NFKBIA mutation were all significantly older (p = 0.05), and the patients with FGF3/4/19/CCND1 amplification were mostly moderately differentiated, and the patients without high differentiation, suggesting a higher degree of malignancy (p = 0.03). CDKN2A, FGF3/4/19/CCND1 amplification, and NFKBIA mutated were associated with a smaller invasion depth, respectively (p = 0,p = 0.03,p = 0.05). Patients with wild type KMT2D had earlier stage, and all N0 stages were wild type for KMT2D (p = 0.03).Notably, high activity of DNA damage,Cell cycle and Notch signaling pathway might be particularly promising strategies for ESCC.In potential therapeutic target analysis, CDKN2A(20.7%) and PIK3CA (13.8%) were the validated and candidate therapeutic targeted genes. Conclusions: Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets.