[与颈动脉体瘤发生相关的新基因]

[Novel Genes Associated with the Development of Carotid Paragangliomas].

作者信息

Snezhkina A V, Lukyanova E N, Fedorova M S, Kalinin D V, Melnikova N V, Stepanov O A, Kiseleva M V, Kaprin A D, Pudova E A, Kudryavtseva A V

机构信息

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.

Vishnevsky Institute of Surgery, Ministry of Health of the Russian Federation, Moscow, 117997 Russia.

出版信息

Mol Biol (Mosk). 2019 Jul-Aug;53(4):613-626. doi: 10.1134/S0026898419040141.

DOI:10.1134/S0026898419040141

PMID:31397435

Abstract

Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors of the head and neck. "Germline" and somatic mutations in a number of genes were shown to be associated with the development of CPGLs; however, molecular mechanisms of the tumor pathogenesis have not been fully understood. In the work, we have used whole exome sequencing data of 52 CPGLs obtained earlier. Using MutSigCV, the search for genes with high mutation rate was performed. Thirty four genes (MADCAM1, SARM1, ZFPM1, CTDSP2, DSPP, POTED, ANP32B, FRG2B, BAGE3, CCDC89, ACOT2, KRTAP10-1, ATXN1, GXYLT1, MUC2, AQP7, TMPRSS13, KRTAP4-3, PRR21, PSPH, PLBD1, ZNF595, IGSF3, PRR16, FAM157A, KCNJ12, HYDIN, IGFBP2, KIAA1671, DISC1, MUC6, XKR3, HRNR, and MUC4) potentially associated with the CPGL initiation and progression were revealed. The involvement of these genes in the pathogenesis of CPGLs was first shown, and possible mechanisms of their participation in that were discussed.

摘要

颈动脉体瘤（CPGLs）是头颈部罕见的神经内分泌肿瘤。已表明一些基因中的“胚系”和体细胞突变与CPGLs的发生发展相关；然而，肿瘤发病机制的分子机制尚未完全明确。在这项研究中，我们使用了先前获得的52例CPGLs的全外显子测序数据。利用MutSigCV，对具有高突变率的基因进行了搜索。发现了34个可能与CPGLs起始和进展相关的基因（MADCAM1、SARM1、ZFPM1、CTDSP2、DSPP、POTED、ANP32B、FRG2B、BAGE3、CCDC89、ACOT2、KRTAP10 - 1、ATXN1、GXYLT1、MUC2、AQP7、TMPRSS13、KRTAP4 - 3、PRR21、PSPH、PLBD1、ZNF595、IGSF3、PRR16、FAM157A、KCNJ12、HYDIN、IGFBP2、KIAA1671、DISC1、MUC6、XKR3、HRNR和MUC4）。首次展示了这些基因参与CPGLs发病机制的情况，并讨论了它们参与其中的可能机制。