Ultra-deep Targeted Sequencing of Advanced Oral Squamous Cell Carcinoma Identifies a Mutation-based Prognostic Gene Signature

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 May 19

PMID 25980437

Citations 33

Authors

Shu-Jen Chen

Hsuan Liu

Chun-Ta Liao

Po-Jung Huang

Yi Huang

An Hsu

Petrus Tang

Yu-Sun Chang

Hua-Chien Chen

Tzu-Chen Yen

Affiliations

Soon will be listed here.

Abstract

Background: Patients with advanced oral squamous cell carcinoma (OSCC) have heterogeneous outcomes that limit the implementation of tailored treatment options. Genetic markers for improved prognostic stratification are eagerly awaited.

Methods: Herein, next-generation sequencing (NGS) was performed in 345 formalin-fixed paraffin-embedded (FFPE) samples obtained from advanced OSCC patients. Genetic mutations on the hotspot regions of 45 cancer-related genes were detected using an ultra-deep (>1000×) sequencing approach. Kaplan-Meier plots and Cox regression analyses were used to investigate the associations between the mutation status and disease-free survival (DFS).

Results: We identified 1269 non-synonymous mutations in 276 OSCC samples. TP53, PIK3CA, CDKN2A, HRAS and BRAF were the most frequently mutated genes. Mutations in 14 genes were found to predict DFS. A mutation-based signature affecting ten genes (HRAS, BRAF, FGFR3, SMAD4, KIT, PTEN, NOTCH1, AKT1, CTNNB1, and PTPN11) was devised to predict DFS. Two different resampling methods were used to validate the prognostic value of the identified gene signature. Multivariate analysis demonstrated that presence of a mutated gene signature was an independent predictor of poorer DFS (P = 0.005).

Conclusions: Genetic variants identified by NGS technology in FFPE samples are clinically useful to predict prognosis in advanced OSCC patients.

Citing Articles

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