title: Inactivating mutations of the caspase-10 gene in gastric cancer.
abstract: 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.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
authors.forename: Jong Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Min Sun
authors.initials: MS
authors.lastname: Shin
authors.forename: Jik Young
authors.initials: JY
authors.lastname: Park
authors.forename: Hong Sug
authors.initials: HS
authors.lastname: Kim
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Young Sil
authors.initials: YS
authors.lastname: Kim
authors.forename: Shi Nae
authors.initials: SN
authors.lastname: Lee
authors.forename: Wenhua
authors.initials: W
authors.lastname: Xiao
authors.forename: Cho Hyun
authors.initials: CH
authors.lastname: Park
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000483:Alleles; D017209:Apoptosis; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics*; D002460:Cell Line; D006801:Humans; D016296:Mutagenesis; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; C506438:CASP10 protein, human