Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways
Abstract. Background:. Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the devel...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2023-11-01
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| Series: | Chinese Medical Journal |
| Online Access: | http://journals.lww.com/10.1097/CM9.0000000000002852 |
| _version_ | 1797449524648607744 |
|---|---|
| author | Shuyuan Wang Zhitao Gu Lei Zhu Yuchen Han Hong Yu Wentao Fang Baohui Han Xiangxiang Pan Peifang Wei |
| author_facet | Shuyuan Wang Zhitao Gu Lei Zhu Yuchen Han Hong Yu Wentao Fang Baohui Han Xiangxiang Pan Peifang Wei |
| author_sort | Shuyuan Wang |
| collection | DOAJ |
| description | Abstract.
Background:. Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches.
Methods:. 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 2017. Patient samples were sequenced using a 324-gene platform with licensed technologies. In 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 TNENs.
Results:. The mutational profiles between TCs and TNENs were diverse. The 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 TSC2. Prognostic 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 patients. Further 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) signaling.
Conclusion:. 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. |
| first_indexed | 2024-03-09T14:27:16Z |
| format | Article |
| id | doaj.art-d9d68654f63a4cf88bfa3a4848c36de3 |
| institution | Directory Open Access Journal |
| issn | 0366-6999 2542-5641 |
| language | English |
| last_indexed | 2024-03-09T14:27:16Z |
| publishDate | 2023-11-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Chinese Medical Journal |
| spelling | doaj.art-d9d68654f63a4cf88bfa3a4848c36de32023-11-28T07:08:38ZengWolters KluwerChinese Medical Journal0366-69992542-56412023-11-01136222712272110.1097/CM9.0000000000002852202311200-00008Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathwaysShuyuan Wang0Zhitao Gu1Lei Zhu2Yuchen Han3Hong Yu4Wentao Fang5Baohui Han6Xiangxiang PanPeifang Wei1 Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China2 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China3 Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China3 Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China4 Department of Radiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.2 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China1 Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, ChinaAbstract. Background:. Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches. Methods:. 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 2017. Patient samples were sequenced using a 324-gene platform with licensed technologies. In 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 TNENs. Results:. The mutational profiles between TCs and TNENs were diverse. The 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 TSC2. Prognostic 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 patients. Further 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) signaling. Conclusion:. 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.http://journals.lww.com/10.1097/CM9.0000000000002852 |
| spellingShingle | Shuyuan Wang Zhitao Gu Lei Zhu Yuchen Han Hong Yu Wentao Fang Baohui Han Xiangxiang Pan Peifang Wei Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways Chinese Medical Journal |
| title | Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways |
| title_full | Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways |
| title_fullStr | Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways |
| title_full_unstemmed | Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways |
| title_short | Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways |
| title_sort | genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways |
| url | http://journals.lww.com/10.1097/CM9.0000000000002852 |
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