PMID- 37749819
OWN - NLM
STAT- MEDLINE
DCOM- 20231130
LR  - 20231130
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 136
IP  - 22
DP  - 2023 Nov 20
TI  - Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms 
      denote prognosis signatures and pathways.
PG  - 2712-2721
LID - 10.1097/CM9.0000000000002852 [doi]
AB  - 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.
CI  - Copyright (c) 2023 The Chinese Medical Association, produced by Wolters Kluwer, 
      Inc. under the CC-BY-NC-ND license.
FAU - Wang, Shuyuan
AU  - Wang S
AD  - Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
FAU - Gu, Zhitao
AU  - Gu Z
AD  - Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai 200030, China.
FAU - Zhu, Lei
AU  - Zhu L
AD  - Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University 
      School of Medicine, Shanghai 200030, China.
FAU - Han, Yuchen
AU  - Han Y
AD  - Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University 
      School of Medicine, Shanghai 200030, China.
FAU - Yu, Hong
AU  - Yu H
AD  - Department of Radiology, Shanghai Chest Hospital, Shanghai Jiao Tong University 
      School of Medicine, Shanghai 200030, China.
FAU - Fang, Wentao
AU  - Fang W
AD  - Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai 200030, China.
FAU - Han, Baohui
AU  - Han B
AD  - Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
LA  - eng
PT  - Journal Article
DEP - 20230925
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - 0 (Proto-Oncogene Proteins)
RN  - Thymic epithelial tumor
SB  - IM
MH  - Humans
MH  - *Thymoma
MH  - Protein-Tyrosine Kinases/genetics
MH  - Proto-Oncogene Proteins/genetics
MH  - China
MH  - *Thymus Neoplasms/genetics/pathology
MH  - Prognosis
MH  - *Neuroendocrine Tumors/genetics/pathology
MH  - Mutation/genetics
PMC - PMC10684125
COIS- None.
EDAT- 2023/09/26 06:43
MHDA- 2023/11/30 06:42
PMCR- 2023/11/20
CRDT- 2023/09/26 00:33
PHST- 2023/04/10 00:00 [received]
PHST- 2023/11/30 06:42 [medline]
PHST- 2023/09/26 06:43 [pubmed]
PHST- 2023/09/26 00:33 [entrez]
PHST- 2023/11/20 00:00 [pmc-release]
AID - 00029330-990000000-00812 [pii]
AID - CMJ-2022-3113 [pii]
AID - 10.1097/CM9.0000000000002852 [doi]
PST - ppublish
SO  - Chin Med J (Engl). 2023 Nov 20;136(22):2712-2721. doi: 
      10.1097/CM9.0000000000002852. Epub 2023 Sep 25.