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

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Chinese Medical Journal 2023年第22期136卷 2712-2721页

作者： Shuyuan Wang Zhitao Gu Lei Zhu Yuchen Han Hong Yu Wentao Fang Baohui Han Department of Respiratory and Critical Care Medicine Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Department of Thoracic Surgery Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Department of Pathology Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Department of Radiology Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China

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.

关键词： Mutational profile Thymic carcinomas Thymic neuroendocrine neoplasms pathologic subtypes Prognosis Thymic malignancy

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