Inactivating mutations of the caspase-10 gene in gastric cancer

被引:74
作者
Park, WS
Lee, JH
Shin, MS
Park, JY
Kim, HS
Lee, JH
Kim, YS
Lee, SN
Xiao, WH
Park, CH
Lee, SH
Yoo, NJ
Lee, JY [1 ]
机构
[1] Catholic Univ Korea, Coll Med, Dept Pathol, Seoul 137701, South Korea
[2] Catholic Univ Korea, Coll Med, Dept Surg, Seoul 137701, South Korea
关键词
caspase-10; mutation; LOH; gastric cancer; apoptosis;
D O I
10.1038/sj.onc.1205394
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have analysed the genetic alteration of the entire coding region and all splice sites of caspase-8 and -10 genes in 99 gastric cancers by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and sequencing. We found LOH of the caspase-8 and -10 in nine (28%) of 32 and in four (15%) of 26 informative cases, respectively. Overall, three of 99 gastric cancers (3%) were found to have the caspase-10 mutations, which were identified in the coding regions of the death effector domain (codon 147) and the p17 large protease domain (codons 257 and 410), whereas no mutation was detected in caspase-8. In vitro expression studies, the M147T and Q257stop mutants severely impaired caspase-10-mediated apoptosis, whereas the V410I which was the same mutation detected in ALPS patient had a significant, albeit less severe, effect on apoptosis. The data presented here suggest that somatic alterations of the caspase-10 gene might contribute to the pathogenesis in a subset of gastric cancers through the loss of their apoptotic function.
引用
收藏
页码:2919 / 2925
页数:7
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