通过筛选碱基特异性突变鉴定33个候选癌基因。

Identification of 33 candidate oncogenes by screening for base-specific mutations.

作者信息

Tuupanen S, Hänninen U A, Kondelin J, von Nandelstadh P, Cajuso T, Gylfe A E, Katainen R, Tanskanen T, Ristolainen H, Böhm J, Mecklin J-P, Järvinen H, Renkonen-Sinisalo L, Andersen C L, Taipale M, Taipale J, Vahteristo P, Lehti K, Pitkänen E, Aaltonen L A

机构信息

1] Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki 00014, Finland [2] Research Programs Unit, Genome-Scale Biology Research Program, University of Helsinki, Biomedicum, PO Box 63 (Haartmaninkatu 8), Helsinki FIN-00014, Finland.

Research Programs Unit, Genome-Scale Biology Research Program, University of Helsinki, Biomedicum, PO Box 63 (Haartmaninkatu 8), Helsinki FIN-00014, Finland.

出版信息

Br J Cancer. 2014 Oct 14;111(8):1657-62. doi: 10.1038/bjc.2014.429. Epub 2014 Aug 12.

DOI:10.1038/bjc.2014.429

PMID:25117815

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4200084/

Abstract

BACKGROUND

Genes with recurrent codon-specific somatic mutations are likely drivers of tumorigenesis and potential therapeutic targets. Hypermutable cancers may represent a sensitive system for generation and selection of oncogenic mutations.

METHODS

We utilised exome-sequencing data on 25 sporadic microsatellite-instable (MSI) colorectal cancers (CRCs) and searched for base-specific somatic mutation hotspots.

RESULTS

We identified novel mutation hotspots in 33 genes. Fourteen genes displayed mutations in the validation set of 254 MSI CRCs: ANTXR1, MORC2, CEP135, CRYBB1, GALNT9, KRT82, PI15, SLC36A1, CNTF, GLDC, MBTPS1, OR9Q2, R3HDM1 and TTPAL. A database search found examples of the hotspot mutations in multiple cancer types.

CONCLUSIONS

This work reveals a variety of new recurrent candidate oncogene mutations to be further scrutinised as potential therapeutic targets.

摘要

背景

具有复发性密码子特异性体细胞突变的基因可能是肿瘤发生的驱动因素和潜在的治疗靶点。高度可变的癌症可能是产生和选择致癌突变的敏感系统。

方法

我们利用了25例散发性微卫星不稳定（MSI）结直肠癌（CRC）的外显子测序数据，并寻找碱基特异性体细胞突变热点。

结果

我们在33个基因中鉴定出了新的突变热点。14个基因在254例MSI CRC验证集中出现了突变：ANTXR1、MORC2、CEP135、CRYBB1、GALNT9、KRT82、PI15、SLC36A1、CNTF、GLDC、MBTPS1、OR9Q2、R3HDM1和TTPAL。数据库搜索发现多种癌症类型中存在热点突变的例子。

结论

这项工作揭示了多种新的复发性候选癌基因突变，作为潜在的治疗靶点有待进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acbf/4200084/f8baef7ea5de/bjc2014429f1.jpg

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通过筛选碱基特异性突变鉴定33个候选癌基因。

Identification of 33 candidate oncogenes by screening for base-specific mutations.

作者信息

机构信息

Research Programs Unit, Genome-Scale Biology Research Program, University of Helsinki, Biomedicum, PO Box 63 (Haartmaninkatu 8), Helsinki FIN-00014, Finland.