具有微卫星不稳定性的人类结直肠癌细胞中候选癌基因的鉴定。

Identification of candidate oncogenes in human colorectal cancers with microsatellite instability.

机构信息

Department of Medical Genetics, University of Helsinki, Helsinki, Finland.

出版信息

Gastroenterology. 2013 Sep;145(3):540-3.e22. doi: 10.1053/j.gastro.2013.05.015. Epub 2013 May 16.

DOI:10.1053/j.gastro.2013.05.015

Abstract

Microsatellite instability can be found in approximately 15% of all colorectal cancers. To detect new oncogenes we sequenced the exomes of 25 colorectal tumors and respective healthy colon tissue. Potential mutation hot spots were confirmed in 15 genes; ADAR, DCAF12L2, GLT1D1, ITGA7, MAP1B, MRGPRX4, PSRC1, RANBP2, RPS6KL1, SNCAIP, TCEAL6, TUBB6, WBP5, VEGFB, and ZBTB2; these were validated in 86 tumors with microsatellite instability. ZBTB2, RANBP2, and PSRC1 also were found to contain hot spot mutations in the validation set. The form of ZBTB2 associated with colorectal cancer increased cell proliferation. The mutation hot spots might be used to develop personalized tumor profiling and therapy.

摘要

微卫星不稳定性大约存在于所有结直肠癌的 15%中。为了检测新的癌基因，我们对 25 个结直肠肿瘤及其相应的健康结肠组织进行了外显子组测序。在 15 个基因中确认了潜在的突变热点；ADAR、 DCAF12L2、GLT1D1、ITGA7、MAP1B、MRGPRX4、PSRC1、RANBP2、RPS6KL1、SNCAIP、TCEAL6、TUBB6、WBP5、VEGFB 和 ZBTB2；这些基因在 86 个存在微卫星不稳定性的肿瘤中得到了验证。在验证集中还发现了 ZBTB2、RANBP2 和 PSRC1 含有热点突变。与结直肠癌相关的 ZBTB2 形式增加了细胞增殖。这些突变热点可能被用于开发个性化的肿瘤分析和治疗。