title: Mutational analysis of caspase 1, 4, and 5 genes in common human cancers.
abstract: Mounting evidence indicates that deregulation of apoptosis is involved in the mechanisms of cancer development. Mutations of genes encoding caspases, the executioners of apoptosis, have been detected in human cancers, indicating inactivation of apoptosis by the mutations of caspase is an important mechanism in cancer development. The aim of this study was to see whether genes encoding human caspases 1, 4, and 5 are mutated in human cancers. We analyzed the entire coding region and all splice sites of human caspase 1, 4, and 5 genes for the detection of somatic mutations in 337 human cancers, including 103 colorectal, 54 gastric, 60 breast, 60 hepatocellular, and 60 lung carcinomas by a single-strand conformation polymorphism assay. We detected 2 (0.6%) caspase-1, 2 (0.6%) caspase-4, and 15 (4.4%) caspase-5 mutations in the 343 cancers. The mutations were detected in 11 gastric carcinomas (2 caspase-1 and 9 caspase-5 mutations), 6 colorectal carcinomas (2 caspase-4 and 4 caspase-5 mutations), 1 breast carcinoma (1 caspase-5 mutation), and 1 lung carcinoma (1 caspase-5 mutation). The mutations consisted of 11 mutations in exons and 8 mutations in noncoding sequences. The 11 mutations in the exons consisted of 3 missense, 1 silent, and 7 frameshift mutation(s). Of note, most (6/9) of the caspase-5 mutations in the coding sequences were detected in microsatellite instability (MSI)-positive cancers. These data indicate that somatic mutations of caspase-1 and caspase-4 genes are rare in common solid cancers. In addition, the data indicate that caspase-5 gene is commonly mutated in the MSI-positive cancers, and suggest that inactivation of caspase-5 may play a role in the tumorigenesis of MSI-positive cancers.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
authors.forename: Young Hwa
authors.initials: YH
authors.lastname: Soung
authors.forename: Eun Goo
authors.initials: EG
authors.lastname: Jeong
authors.forename: Chang Hyeok
authors.initials: CH
authors.lastname: Ahn
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Song
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D020170:Caspase 1 / Q000235:genetics*; D020169:Caspases / Q000235:genetics*; D053471:Caspases, Initiator / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; C093516:CASP4 protein, human; C099217:CASP5 protein, human; D020169:Caspases; D053471:Caspases, Initiator; D020170:Caspase 1