Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways

作     者：Shuyuan Wang Zhitao Gu Lei Zhu Yuchen Han Hong Yu Wentao Fang Baohui Han 

作者机构：Department of Respiratory and Critical Care MedicineShanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Department of Thoracic SurgeryShanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Department of PathologyShanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Department of RadiologyShanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2023年第136卷第22期

页      面：2712-2721页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China(No.82272913) National Multi-disciplinary Treatment Project for Major Disease(No.2020NMDTP) Shanghai Sailing Program of Science and Technology Commission of Shanghai Municipality(No.20YF1428100) Interdisciplinary Program of Shanghai Jiao Tong University(No.YG2021QN126) Shanghai Chest Hospital(No.2020YNJCM10) 

主　　题：Mutational profile Thymic carcinomas Thymic neuroendocrine neoplasms Pathologic subtypes Prognosis Thymic malignancy 

摘      要：Background:Thymic carcinomas(TCs)and thymic neuroendocrine neoplasms(TNENs)are two aggressive subtypes of thymic *** therapy for advanced TCs and TNENs has limited *** genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment ***:We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and *** samples were sequenced using a 324-gene platform with licensed *** this study,we focused on clinically relevant genomic alterations(CRGAs),which are previously proven to be pathogenic alterations,to identify the pathology-specific mutational patterns,prognostic signatures of TCs and ***:The mutational profiles between TCs and TNENs were *** genetic alterations that ranked highest in TCs were in CDKN2A,TP53,ASXL1,CDKN2B,PIK3C2G,PTCH1,and ROS1,while those in TNENs were in MEN1,MLL2,APC,RB1,and *** analysis showed that mutations of ROS1,CDKN2A,CDKN2B,BRAF,and BAP1 were significantly associated with worse outcomes in TC patients,and that mutation of ERBB2 indicated shortened disease-free survival(DFS)and overall survival(OS)in TNEN *** investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control,chromatin remodeling/DNA methylation,phosphoinositide 3-kinases(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR),and receptor tyrosine kinase(RTK)/RAS/mitogen-activated protein kinase(MAPK)***:We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors,and identified the pathology-specific mutational patterns,prognostic signatures,and potential therapeutic targets for TCs and TNENs.