title: Inactivating mutations of CASPASE-7 gene in human cancers.
abstract: Caspase-7 is a caspase involved in the execution phase of apoptosis. To explore the possibility that the genetic alterations of CASPASE-7 might be involved in the development of human cancers, we analysed the entire coding region and all splice sites of human CASPASE-7 gene for the detection of somatic mutations in a series of human solid cancers, including carcinomas from stomach, colon, head/neck, esophagus, urinary bladder and lung. Overall, we detected CASPASE-7 mutations in two of 98 colon carcinomas (2.0%), one of 50 esophageal carcinomas (2.0%) and one of 33 head/neck carcinomas (3.0%). We expressed the tumor-derived caspase-7 mutants in 293 T cells and found that the apoptosis was reduced compared to the wild-type caspase-7. This is the first report on the CASPASE-7 gene mutations in human malignancies, and our data suggest that the inactivating mutations of the CASPASE-7 gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some human solid cancers.
authors.affiliation: College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, Korea.
authors.forename: Young Hwa
authors.initials: YH
authors.lastname: Soung
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Hong Sug
authors.initials: HS
authors.lastname: Kim
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
authors.forename: Su Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Jong Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Jik Young
authors.initials: JY
authors.lastname: Park
authors.forename: Yong Gu
authors.initials: YG
authors.lastname: Cho
authors.forename: Chang Jae
authors.initials: CJ
authors.lastname: Kim
authors.forename: Yong Gyu
authors.initials: YG
authors.lastname: Park
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
authors.forename: Seong Whan
authors.initials: SW
authors.lastname: Jeong
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics; D053179:Caspase 7; D020169:Caspases / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics; D020868:Gene Silencing; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D019656:Loss of Heterozygosity; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: C505520:CASP7 protein, human; D053179:Caspase 7; D020169:Caspases