Graduate Department of Bioconvergence Science and Technology, Dankook University, Jukjeon, Yongin, Gyeonggi 16890, Korea.
Mol Cells. 2019 Jan 31;42(1):8-16. doi: 10.14348/molcells.2018.0436. Epub 2019 Jan 7.
Mutations in the β-catenin gene () have been implicated in the pathogenesis of some cancers. The recent development of cancer genome databases has facilitated comprehensive and focused analyses on the mutation status of cancer-related genes. We have used these databases to analyze the mutations assembled from different tumor types. High incidences of mutations were detected in endometrial, liver, and colorectal cancers. This finding agrees with the oncogenic role of aberrantly activated β-catenin in epithelial cells. Elevated frequencies of missense mutations were found in the exon 3 of , which is responsible for encoding the regulatory amino acids at the N-terminal region of the protein. In the case of metastatic colorectal cancers, inframe deletions were revealed in the region spanning exon 3. Thus, exon 3 of can be considered to be a mutation hotspot in these cancers. Since the N-terminal region of the β-catenin protein forms a flexible structure, many questions arise regarding the structural and functional impacts of hotspot mutations. Clinical identification of hotspot mutations could provide the mechanistic basis for an oncogenic role of mutant β-catenin proteins in cancer cells. Furthermore, a systematic understanding of tumor-driving hotspot mutations could open new avenues for precision oncology.
β-连环蛋白基因（）中的突变与一些癌症的发病机制有关。最近癌症基因组数据库的发展促进了对癌症相关基因突变状态的全面和有针对性的分析。我们使用这些数据库分析了来自不同肿瘤类型的 突变。在子宫内膜癌、肝癌和结直肠癌中检测到 突变的高发率。这一发现与异常激活的β-连环蛋白在上皮细胞中的致癌作用一致。在负责编码蛋白质 N 端区域调节氨基酸的外显子 3 中发现了错义突变的高频。在转移性结直肠癌的情况下，在跨越外显子 3 的区域中发现了框内缺失。因此，外显子 3 可以被认为是这些癌症中的突变热点。由于β-连环蛋白蛋白的 N 端区域形成了一个灵活的结构，因此出现了许多关于热点突变的结构和功能影响的问题。对热点突变的临床鉴定可以为突变β-连环蛋白蛋白在癌细胞中的致癌作用提供机制基础。此外，对肿瘤驱动热点突变的系统理解可以为精准肿瘤学开辟新途径。
