SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors

Penghui Yang; Xuanlin Huang; Chengcai Lai; Lin Li; Tieling Li; Peide Huang; Songying Ouyang; Jin Yan; Sijie Cheng; Guanglin Lei; Zhaohai Wang; Linxiang Yu; Zhixian Hong; Ruisheng Li; Hui Dong; Cheng Wang; Yinghao Yu; Xuan Wang; Xianghong Li; Liming Wang; Fudong Lv; Ye Yin; Huanming Yang; Jianxun Song; Qiang Gao; Xiliang Wang; Shaogeng Zhang

doi:10.1002/ijc.32334

SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors

Penghui Yang, Xuanlin Huang, Chengcai Lai, Lin Li, Tieling Li, Peide Huang, Songying Ouyang, Jin Yan, Sijie Cheng, Guanglin Lei, Zhaohai Wang, Linxiang Yu, Zhixian Hong, Ruisheng Li, Hui Dong, Cheng Wang, Yinghao Yu, Xuan Wang, Xianghong Li, Liming WangFudong Lv, Ye Yin, Huanming Yang, Jianxun Song, Qiang Gao^*, Xiliang Wang, Shaogeng Zhang

^*Corresponding author af dette arbejde

4 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	International Journal of Cancer
Vol/bind	145
Udgave nummer	11
Sider (fra-til)	2986-2995
ISSN	0020-7136
DOI	https://doi.org/10.1002/ijc.32334
Status	Udgivet - 1 dec. 2019

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10.1002/ijc.32334

ijc.32334Forlagets udgivne version, 1,26 MB

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Yang, P., Huang, X., Lai, C., Li, L., Li, T., Huang, P., Ouyang, S., Yan, J., Cheng, S., Lei, G., Wang, Z., Yu, L., Hong, Z., Li, R., Dong, H., Wang, C., Yu, Y., Wang, X., Li, X., ... Zhang, S. (2019). SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors. International Journal of Cancer, 145(11), 2986-2995. https://doi.org/10.1002/ijc.32334

Yang, P, Huang, X, Lai, C, Li, L, Li, T, Huang, P, Ouyang, S, Yan, J, Cheng, S, Lei, G, Wang, Z, Yu, L, Hong, Z, Li, R, Dong, H, Wang, C, Yu, Y, Wang, X, Li, X, Wang, L, Lv, F, Yin, Y, Yang, H, Song, J, Gao, Q, Wang, X & Zhang, S 2019, 'SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors', International Journal of Cancer, bind 145, nr. 11, s. 2986-2995. https://doi.org/10.1002/ijc.32334

@article{d345a881176a4c2796170bd7f5e65fb3,

title = "SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors",

abstract = "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.",

keywords = "PHNETs, SETD1B, whole-exome sequencing",

author = "Penghui Yang and Xuanlin Huang and Chengcai Lai and Lin Li and Tieling Li and Peide Huang and Songying Ouyang and Jin Yan and Sijie Cheng and Guanglin Lei and Zhaohai Wang and Linxiang Yu and Zhixian Hong and Ruisheng Li and Hui Dong and Cheng Wang and Yinghao Yu and Xuan Wang and Xianghong Li and Liming Wang and Fudong Lv and Ye Yin and Huanming Yang and Jianxun Song and Qiang Gao and Xiliang Wang and Shaogeng Zhang",

year = "2019",

month = dec,

day = "1",

doi = "10.1002/ijc.32334",

language = "English",

volume = "145",

pages = "2986--2995",

journal = "Radiation Oncology Investigations",

issn = "0020-7136",

publisher = "JohnWiley & Sons, Inc.",

number = "11",

}

TY - JOUR

T1 - SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors

AU - Yang, Penghui

AU - Huang, Xuanlin

AU - Lai, Chengcai

AU - Li, Lin

AU - Li, Tieling

AU - Huang, Peide

AU - Ouyang, Songying

AU - Yan, Jin

AU - Cheng, Sijie

AU - Lei, Guanglin

AU - Wang, Zhaohai

AU - Yu, Linxiang

AU - Hong, Zhixian

AU - Li, Ruisheng

AU - Dong, Hui

AU - Wang, Cheng

AU - Yu, Yinghao

AU - Wang, Xuan

AU - Li, Xianghong

AU - Wang, Liming

AU - Lv, Fudong

AU - Yin, Ye

AU - Yang, Huanming

AU - Song, Jianxun

AU - Gao, Qiang

AU - Wang, Xiliang

AU - Zhang, Shaogeng

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

KW - PHNETs

KW - SETD1B

KW - whole-exome sequencing

U2 - 10.1002/ijc.32334

DO - 10.1002/ijc.32334

M3 - Journal article

C2 - 30977120

AN - SCOPUS:85066035026

SN - 0020-7136

VL - 145

SP - 2986

EP - 2995

JO - Radiation Oncology Investigations

JF - Radiation Oncology Investigations

IS - 11

ER -

SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors

Abstract

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