PMID- 33428730
OWN - NLM
STAT- MEDLINE
DCOM- 20211019
LR  - 20221207
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 106
IP  - 4
DP  - 2021 Mar 25
TI  - Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer.
PG  - 988-998
LID - 10.1210/clinem/dgab014 [doi]
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and 
      few systematic investigations on genomic profiles of ATC have been performed in 
      Chinese patients. METHODS: Fifty-four ATC patients in West China Hospital between 
      2010 to 2020 were retrospectively analyzed, while 29 patients with available 
      samples were sequenced by whole-exome sequencing (WES). The associations between 
      genomic alterations and clinical characteristics were statistically evaluated. 
      RESULTS: The median overall survival was 3.0 months in the entire cohort, which 
      was impacted by multiple clinical features, including age, tumor size, and 
      different treatment strategies. In the WES cohort, totally 797 nonsilent 
      mutations were detected; the most frequently altered genes were TP53 (48%), BRAF 
      (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been 
      well-reported in previous studies, ethnic specificity was exhibited in terms of 
      mutation frequency. Moreover, several novel significantly mutated genes were 
      identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 
      (10%). WES-based copy number alteration analysis also revealed a high frequent 
      gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations 
      and copy number alterations were enriched in phosphatidylinositol 
      3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. 
      CONCLUSIONS: This study reveals shared and ethnicity-specific genomic profiles of 
      ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver 
      gene for ATC tumorigenesis.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      Endocrine Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Zhang, Lingyun
AU  - Zhang L
AD  - Department of Thyroid and Parathyroid Surgery, Laboratory of thyroid and 
      parathyroid disease, Frontiers Science Center for Disease-related Molecular 
      Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
AD  - West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
FAU - Ren, Zhixiang
AU  - Ren Z
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, Sichuan, China.
AD  - Department of Laboratory Medicine, Precision Medicine Center, State Key 
      Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Su, Zhengzheng
AU  - Su Z
AD  - Department of Pathology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Liu, Yang
AU  - Liu Y
AD  - Department of Thyroid and Parathyroid Surgery, Laboratory of thyroid and 
      parathyroid disease, Frontiers Science Center for Disease-related Molecular 
      Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
AD  - West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
FAU - Yang, Tian
AU  - Yang T
AD  - West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
AD  - Department of Pathology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Cao, Minyuan
AU  - Cao M
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Jiang, Yong
AU  - Jiang Y
AD  - Department of Pathology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Tang, Ying
AU  - Tang Y
AD  - Department of Pathology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Chen, Haining
AU  - Chen H
AD  - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 
      Chengdu, Sichuan, China.
FAU - Zhang, Weihan
AU  - Zhang W
AD  - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 
      Chengdu, Sichuan, China.
FAU - Gong, Rixiang
AU  - Gong R
AD  - Department of Thyroid and Parathyroid Surgery, Laboratory of thyroid and 
      parathyroid disease, Frontiers Science Center for Disease-related Molecular 
      Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
FAU - Wei, Tao
AU  - Wei T
AD  - Department of Thyroid and Parathyroid Surgery, Laboratory of thyroid and 
      parathyroid disease, Frontiers Science Center for Disease-related Molecular 
      Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
FAU - Peng, Yong
AU  - Peng Y
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Liu, Bo
AU  - Liu B
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, 
      Xiangya Hospital, Central South University, Changsha, China.
FAU - Yang, Li
AU  - Yang L
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Hu, Yiguo
AU  - Hu Y
AD  - Department of Thyroid and Parathyroid Surgery, Laboratory of thyroid and 
      parathyroid disease, Frontiers Science Center for Disease-related Molecular 
      Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Li, Zhihui
AU  - Li Z
AD  - Department of Thyroid and Parathyroid Surgery, Laboratory of thyroid and 
      parathyroid disease, Frontiers Science Center for Disease-related Molecular 
      Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
FAU - Zhu, Jingqiang
AU  - Zhu J
AD  - Department of Thyroid and Parathyroid Surgery, Laboratory of thyroid and 
      parathyroid disease, Frontiers Science Center for Disease-related Molecular 
      Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
FAU - Xu, Heng
AU  - Xu H
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, Sichuan, China.
AD  - Department of Laboratory Medicine, Precision Medicine Center, State Key 
      Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Shu, Yang
AU  - Shu Y
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, Sichuan, China.
AD  - Department of Laboratory Medicine, Precision Medicine Center, State Key 
      Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Luo, Han
AU  - Luo H
AD  - Department of Thyroid and Parathyroid Surgery, Laboratory of thyroid and 
      parathyroid disease, Frontiers Science Center for Disease-related Molecular 
      Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (PIK3CA protein, human)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 2.7.7.49 (TERT protein, human)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Asian People/genetics/statistics & numerical data
MH  - China/epidemiology
MH  - Class I Phosphatidylinositol 3-Kinases/genetics
MH  - Cohort Studies
MH  - DNA Mutational Analysis/methods
MH  - Female
MH  - Gene Frequency
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - Retrospective Studies
MH  - Telomerase/genetics
MH  - Thyroid Carcinoma, Anaplastic/ethnology/*genetics/pathology
MH  - Thyroid Neoplasms/ethnology/*genetics/pathology
MH  - Tumor Suppressor Protein p53/genetics
MH  - Whole Genome Sequencing
OTO - NOTNLM
OT  - NOTCH2NL
OT  - anaplastic thyroid cancer
OT  - ethnicity-specific
OT  - genomic profile
OT  - whole-exome sequencing
EDAT- 2021/01/12 06:00
MHDA- 2021/10/21 06:00
CRDT- 2021/01/11 17:11
PHST- 2020/09/04 00:00 [received]
PHST- 2021/01/12 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2021/01/11 17:11 [entrez]
AID - 6082745 [pii]
AID - 10.1210/clinem/dgab014 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2021 Mar 25;106(4):988-998. doi: 10.1210/clinem/dgab014.