Lee Jong Woo, Kim Mee Ran, Soung Young Hwa, Nam Suk Woo, Kim Sang Ho, Lee Jung Young, Yoo Nam Jin, Lee Sug Hyung
Department of Pathology, The Catholic University of Korea, Seoul, Korea.
APMIS. 2006 Sep;114(9):646-50. doi: 10.1111/j.1600-0463.2006.apm_417.x.
Failure of apoptosis is one of the hallmarks of cancer. As an execution-phase caspase, caspase-6 plays a crucial role during apoptosis. To explore the possibility that the genetic alterations of CASP, which encodes caspase-6, might be involved in the development of human cancers, we analyzed the entire coding region and all splice sites of the human CASP6 gene for the detection of somatic mutations in 100 colorectal carcinomas and 50 gastric carcinomas. Overall, we detected three somatic mutations of the CASP6 gene, including two missense mutations and one splice-site mutation. The mutations were observed in two of the 100 colorectal carcinomas (2.0%) and one of the 50 gastric carcinomas (2.0%). Of note, one colorectal carcinoma with the CASP6 mutation harbored CASP3 and CASP8 gene mutations as well. We also analyzed caspase-6 expression by immunohistochemistry, and found that caspase-6 was expressed in 60% of the gastric cancers and 90% of the colorectal cancers. This is the first report on CASP6 gene mutations in human cancers, and these data indicate that the CASP6 gene is occasionally mutated in gastric and colorectal carcinomas. Also, the data suggest the possibility that deficiency of caspase-6 expression might contribute to the pathogenesis of gastric cancers.
细胞凋亡失败是癌症的标志之一。作为一种执行阶段的半胱天冬酶，半胱天冬酶-6在细胞凋亡过程中起着关键作用。为了探究编码半胱天冬酶-6的CASP基因的遗传改变可能参与人类癌症发生发展的可能性，我们分析了人类CASP6基因的整个编码区和所有剪接位点，以检测100例结直肠癌和50例胃癌中的体细胞突变。总体而言，我们检测到了CASP6基因的3个体细胞突变，包括2个错义突变和1个剪接位点突变。在100例结直肠癌中有2例（2.0%）以及50例胃癌中有1例（2.0%）观察到了这些突变。值得注意的是，1例携带CASP6突变的结直肠癌还同时存在CASP3和CASP8基因突变。我们还通过免疫组织化学分析了半胱天冬酶-6的表达，发现半胱天冬酶-6在60%的胃癌和90%的结直肠癌中表达。这是关于人类癌症中CASP6基因突变的首次报道，这些数据表明CASP6基因在胃癌和结直肠癌中偶尔会发生突变。此外，这些数据提示半胱天冬酶-6表达缺失可能参与胃癌发病机制的可能性。
