中國人民解放軍總醫院第五醫學中心肝臟罕見腫瘤領域重磅研究

近日，腫瘤學領域老牌雜誌International Journal of Cancer在線發表了中國人民解放軍總醫院第五醫學中心肝膽外科團隊完成的一項肝臟罕見腫瘤研究成果「SET domain containing 1B gene(SETD1B) is mutated in primary hepatic neuroendocrine tumors」該研究採用全外顯子測序，對來自全國26家醫院的肝臟原發神經內分泌腫瘤（Primaryhepatic neuroendocrine tumors, PHNETs)）樣本進行了WES測序分析，發現SETD1B基因具有和TP53相同的突變頻率，且顯著高於其餘基因，接著分析了SETD1B基因信息、保守性、空間結構預測、資料庫信息，進一步針對SETD1B基因出現的3種突變形式（S487L、C931Y、A1054del）開展了功能研究，結合患者臨床信息得出結論SETD1B基因突變患者預後更差，有望成為PHNET潛在的診斷、預後分子標誌物及治療藥物靶標。

神經內分泌腫瘤（Neuroendocrine tumors, NET）是起源於肽能神經元和神經內分泌細胞的異質性腫瘤。NETs全身均能發生，而發生在肝臟的原發神經內分泌腫瘤十分罕見，約佔NETs的0.3%。本研究首次構建了肝臟原發神經內分泌腫瘤的突變譜，使得對其腫瘤生物學的有了全方位認識，並提出了針對它的潛在的診斷標誌物和藥物靶標。

Whole-exomesequencing and mutated genes in 22 patients with PHNETs

通訊作者為張紹庚主任醫師、王希良研究員、高強教授！第一作者為解放軍總醫院第五醫學中心楊鵬輝、華大基因黃宣林、軍事醫學研究院賴成材、華大基因李林！

Abstract

Primaryhepatic neuroendocrine tumors (PHNETs) are extremely rare NETs originating fromthe liver. These tumors are associated with heterogeneous prognosis, and fewtreatment targets for PHNETs have been identified. Because the major geneticalterations in PHNET are still largely unknown, we performed whole-exomesequencing of 22 paired tissues from PHNET patients and identified 22 recurringmutations of somatic genes involved in the following activities:epigeneticmodification (BPTF, MECP2 and WDR5), cell cycle (TP53, ATM, MED12, DIDO1 andATAD5) and neural development (UBR4, MEN1, GLUL and GIGYF2). Here, we show thatTP53 and the SET domain containing the 1B gene (SETD1B) are the most frequentlymutated genes in this set of samples (3/22 subjects, 13.6%). A biologicalanalysis suggests that one of the three SETD1B mutants, A1054del, promotes cellproliferation, migration and invasion compared with wild-type SETD1B. Our workunveils that SETD1B A1054del mutant is functional in PHNET and implicates genesincluding TP53 in the disease. Our findings thus characterize the mutationallandscapes of PHNET and implicate novel gene mutations linked to PHNETpathogenesis and potential therapeutic targets.

https://onlinelibrary.wiley.com/doi/10.1002/ijc.32334

中國生物技術網誠邀生物領域科學家在我們的平台上，發表和介紹國內外原創的科研成果。

本公眾號由中國科學院微生物研究所信息中心承辦

微信公眾號：中國生物技術網

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