Targeted next-generation sequencing of cancer genes identified frequent TP53 and ATRX mutations in leiomyosarcoma
Journal
American Journal of Translational Research
Journal Volume
7
Journal Issue
10
Pages
2072-2081
Date Issued
2015
Author(s)
Huang W.-J.
Su Y.-N.
Hung C.-C.
Abstract
Leiomyosarcoma is an aggressive soft tissue sarcoma with poor patient survival. The genetic changes of leiomyosarcoma remain to be discovered. In this study, we analyzed the genetic changes of 44 cancer-related genes by using next-generation sequencing in 54 leiomyosarcomas. We identified TP53 mutations in 19 of the 54 tumors (35%) and ATRX mutations in 9 of the 54 tumors (17%). The TP53-mutated leiomyosarcomas were limited to female patients (P = 0.006). All but 2 of the TP53-mutated leiomyosarcomas were located in the uterus (n = 11) or retroperitoneum (n = 6). The ATRX mutations were associated with poorly differentiated leiomyosarcomas (P = 0.028) and the presence of tumor necrosis (P = 0.015). Kaplan-Meier survival analysis showed that patients with ATRX-mutated leiomyosarcomas had worse overall survival than did patients with ATRX-wild-type leiomyosarcomas. All of the ATRX-mutated leiomyosarcomas showed the alternative lengthening of telomere phenotype. The ATRX mutations did not correlate with ATRX protein expression, as detected using immunohistochemistry. In conclusion, we identified loss of function of the p53 and ATRX pathways being the main mechanisms for leiomyosarcomas. The molecular mechanisms may provide new opportunities to treat these aggressive neoplasms. ? 2015, E-Century Publishing Corporation. All rights reserved.
SDGs
Other Subjects
protein p53; adult; Article; bioinformatics; controlled study; DNA extraction; female; fluorescence in situ hybridization; frameshift mutation; gene mutation; gene sequence; human; human tissue; immunohistochemistry; leiomyosarcoma; loss of function mutation; major clinical study; male; middle aged; next generation sequencing; polymerase chain reaction; prevalence; protein expression; sequence analysis; signal transduction; tumor differentiation; tumor gene; tumor necrosis
Publisher
E-Century Publishing Corporation
Type
journal article