Massively Parallel Sequencing Identifies Recurrent Mutations in TP53 in Thymic Carcinoma Associated with Poor Prognosis

摘要: Background The characterization of the molecular alterations in thymic epithelial tumors may lead to a better understanding tumorigenesis, new therapeutic targets, and biomarkers these tumors. Methods Paired tissue (tumor matched normal) from 15 carcinomas (TCA) six B3 thymomas were evaluated by exon capture 275 cancer-related genes, followed deep coverage next-generation sequencing, which identifies somatic sequence variants, small insertions deletions, copy number involving all exons captured genes. Results Non-silent mutations identified 12 (80%) TCA with median one mutation per tumor (range 0–26). Recurrent suppressor genes TP53 ( n = 4), SMAD4 2), CYLD 2); chromatin remodeling KDM6A 3), SETD2 MLL3 MLL2 2). Tumors appeared exhibit more aggressive behavior. Therefore, role P53 was immunohistochemistry an additional ten cases. overexpression correlated mutation. These had higher rate recurrence death disease compared carcinoma normal p53 expression p 0.02 for disease-free survival 0.05 overall survival). Among thymomas, four Mutations BCOR (BCL6 co-repressor) seen three (involved histone methylation) tumor. Conclusions Next-generation sequencing cancer revealed low frequency mutation, different patterns between thymomas. most frequently mutated respectively. Alterations are associated worse prognosis TCA.