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SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors
Author(s) -
Yang Penghui,
Huang Xuanlin,
Lai Chengcai,
Li Lin,
Li Tieling,
Huang Peide,
Ouyang Songying,
Yan Jin,
Cheng Sijie,
Lei Guanglin,
Wang Zhaohai,
Yu Linxiang,
Hong Zhixian,
Li Ruisheng,
Dong Hui,
Wang Cheng,
Yu Yinghao,
Wang Xuan,
Li Xianghong,
Wang Liming,
Lv Fudong,
Yin Ye,
Yang Huanming,
Song Jianxun,
Gao Qiang,
Wang Xiliang,
Zhang Shaogeng
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32334
Subject(s) - biology , gene , exome sequencing , men1 , epigenetics , somatic cell , cancer research , exome , mutation , mutant , genetics , multiple endocrine neoplasia
Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare NETs originating from the liver. These tumors are associated with heterogeneous prognosis, and few treatment targets for PHNETs have been identified. Because the major genetic alterations in PHNET are still largely unknown, we performed whole‐exome sequencing of 22 paired tissues from PHNET patients and identified 22 recurring mutations of somatic genes involved in the following activities: epigenetic modification ( BPTF , MECP2 and WDR5 ), cell cycle ( TP53 , ATM , MED12 , DIDO1 and ATAD5 ) and neural development ( UBR4 , MEN1 , GLUL and GIGYF2 ). Here, we show that TP53 and the SET domain containing the 1B gene ( SETD1B ) are the most frequently mutated genes in this set of samples (3/22 subjects, 13.6%). A biological analysis suggests that one of the three SETD1B mutants, A1054del, promotes cell proliferation, migration and invasion compared to wild‐type SETD1B . Our work unveils that SETD1B A1054del mutant is functional in PHNET and implicates genes including TP53 in the disease. Our findings thus characterize the mutational landscapes of PHNET and implicate novel gene mutations linked to PHNET pathogenesis and potential therapeutic targets.