胰腺神经内分泌肿瘤病因学及基因分型

韩序; 楼文晖

doi:10.3969/j.issn.1674-9081.2020.04.004

胰腺神经内分泌肿瘤病因学及基因分型

doi: 10.3969/j.issn.1674-9081.2020.04.004

韩序,
楼文晖^,

复旦大学附属中山医院普通外科, 上海 200032

基金项目:

国家自然科学基金 81702304

国家自然科学基金 81773068

详细信息

通讯作者:
楼文晖电话:021-64041990, E-mail:lou.wenhui@zs-hospital.sh.cn

中图分类号: R58
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出版历程
- 收稿日期: 2020-03-27
- 刊出日期: 2020-07-30

Advances in Research on Genotyping and the Molecular Mechanism of Pancreatic Neuroendocrine Neoplasias

Xu HAN,
Wen-hui LOU^,

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China

More Information

Corresponding author: LOU Wen-hui Tel: 86-21-64041990, E-mail:lou.wenhui@zs-hospital.sh.cn

摘要

摘要: 大量研究发现, 染色体重塑相关基因(ATRX/DAXX、ARID1A)、MEN-1基因、DNA损伤修复基因(MUTYH)和哺乳动物雷帕霉素靶蛋白信号通路相关基因的异常改变共同参与了无功能性胰腺神经内分泌肿瘤(pancreatic neuroendocrine neoplasia, pNEN)的发生发展。作为功能性pNEN的代表, 胰岛素瘤常出现拷贝数异常, 伴随转录因子YY1的热点突变。驱动基因突变、DNA损伤修复、DNA甲基化、组蛋白修饰、染色体重塑和端粒替代延长机制激活等表观遗传学的异常改变以及相关信号通路的异常激活协同引起pNEN增殖和侵袭。这些分子机制及基因分型具有十分重要的意义, 可为临床个体化综合治疗和预后判断提供依据, 使更多的pNEN患者从精准医学中获益。
- 神经内分泌肿瘤 /
- 胰腺 /
- 分子机制 /
- 基因突变 /
- 表观遗传学
Abstract: Genomic sequencing studies have led to an increased understanding of the genotyping and molecular biology of pancreatic neuroendocrine neoplasias(pNENs). Recent studies reported that ATRX(α-thalassaemia/mental retardation syndrome X-linked)/DAXX(death-domain associated protein), ARID1A(AT-rich interactive domain-containing protein 1A, BAF250A), MUTYH(mutY homolog), and MEN-1(multiple endocrine neoplasia type 1) genes are remarkably mutated in non-functional pNENs, as well as genes encoding core components of the mammalian target of rapamycin (mTOR) signaling pathway. As a representative of functional pNENs, insulinomas had CNV amplifications and copy neutral with YY1 (Yin Yang 1) gene mutations. These mutated genes are involved in aberrations of chromatin remodeling, DNA damage repair, histone modification, and telomere maintenance, and thus might contribute to tumorigenesis and ultimately to the progression of pNENs characterized by divergent phenotypes. Differentiating genotypic subtypes of pNENs plays an important role in prognostication. Future therapies might be based on recent advances in molecular genotyping and mechanism.
- neuroendocrine neoplasia /
- pancreas /
- molecular mechanism /
- genetics /
- epigenetics
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参考文献(38)

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胰腺神经内分泌肿瘤病因学及基因分型

doi: 10.3969/j.issn.1674-9081.2020.04.004

通讯作者:
楼文晖电话:021-64041990, E-mail:lou.wenhui@zs-hospital.sh.cn

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Advances in Research on Genotyping and the Molecular Mechanism of Pancreatic Neuroendocrine Neoplasias

Corresponding author: LOU Wen-hui Tel: 86-21-64041990, E-mail:lou.wenhui@zs-hospital.sh.cn

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胰腺神经内分泌肿瘤病因学及基因分型

doi: 10.3969/j.issn.1674-9081.2020.04.004

通讯作者: 楼文晖 电话:021-64041990, E-mail:lou.wenhui@zs-hospital.sh.cn

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出版历程

Advances in Research on Genotyping and the Molecular Mechanism of Pancreatic Neuroendocrine Neoplasias

Corresponding author: LOU Wen-hui Tel: 86-21-64041990, E-mail:lou.wenhui@zs-hospital.sh.cn

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出版历程

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通讯作者:
楼文晖电话:021-64041990, E-mail:lou.wenhui@zs-hospital.sh.cn