Inactivating mutations of CASPASE-7 gene in human cancers.
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.
Soung
Young Hwa
YH
College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, Korea.
Lee
Jong Woo
JW
Kim
Hong Sug
HS
Park
Won Sang
WS
Kim
Su Young
SY
Lee
Jong Heun
JH
Park
Jik Young
JY
Cho
Yong Gu
YG
Kim
Chang Jae
CJ
Park
Yong Gyu
YG
Nam
Suk Woo
SW
Jeong
Seong Whan
SW
Kim
Sang Ho
SH
Lee
Jung Young
JY
Yoo
Nam Jin
NJ
Lee
Sug Hyung
SH
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
C505520:CASP7 protein, human; D053179:Caspase 7; D020169:Caspases