title: Targeted next-generation sequencing of cancer genes identified frequent TP53 and ATRX mutations in leiomyosarcoma.
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.
authors.affiliation: Department of Surgery, National Taiwan University Hospital, and National Taiwan University College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Yang
authors.affiliation: Department of Pathology, National Taiwan University Hospital, and Graduate Institute of Pathology, National Taiwan University College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Jau-Yu
authors.initials: JY
authors.lastname: Liau
authors.affiliation: Department of Pathology, National Taiwan University Hospital, and Graduate Institute of Pathology, National Taiwan University College of Medicine, National Taiwan University Taipei, Taiwan ; Department of Nursing, Hsin-Sheng College of Medical Care and Management Taoyuan, Taiwan.
authors.forename: Wei-Ju
authors.initials: WJ
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, and National Taiwan University College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, and National Taiwan University College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Ming-Chu
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Department of Pathology, National Taiwan University Hospital, and Graduate Institute of Pathology, National Taiwan University College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Pathology, National Taiwan University Hospital, and Graduate Institute of Pathology, National Taiwan University College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Jia-Huei
authors.initials: JH
authors.lastname: Tsai
authors.affiliation: Sofiva Genomics, Inc. Taipei, Taiwan.
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.affiliation: Sofiva Genomics, Inc. Taipei, Taiwan.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Hung
authors.affiliation: Department of Pathology, National Taiwan University Hospital, and Graduate Institute of Pathology, National Taiwan University College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
keywords: ATRX; Leiomyosarcoma; TP53; alternative lengthening of telomeres