title: Inactivating mutations of CASP10 gene in non-Hodgkin lymphomas.
abstract: Caspase 10 (Mch4/FLICE2) is a caspase homologous to caspase 8. A recent report described that inherited CASP10 gene mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome (ALPS). In this study, to explore the possibility that mutation of this gene might be involved in the development of non-Hodgkin lymphoma (NHL), we have analyzed the entire coding region and all splice sites of the CASP10 gene for the detection of somatic mutations in 117 human NHLs. Overall, 17 NHLs (14.5%) were found to have CASP10 mutations, which were identified in the coding regions of the prodomain (n = 3), the p17 large protease subunit (n = 11), and the p12 small protease subunit (n = 3). We expressed the tumor-derived caspase 10 mutants in 293 cells and found that apoptosis was suppressed. These data suggest that the inactivating mutations of the CASP10 gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some human NHLs.
authors: Department of PathologyCollege of Medicine, The Catholic University of Korea, Seoul, Korea.
authors: Min Sun
authors: MS
authors: Shin
authors: Hong Sug
authors: HS
authors: Kim
authors: Chang Suk
authors: CS
authors: Kang
authors: Won Sang
authors: WS
authors: Park
authors: Su Young
authors: SY
authors: Kim
authors: Shi Nae
authors: SN
authors: Lee
authors: Jong Heun
authors: JH
authors: Lee
authors: Jik Young
authors: JY
authors: Park
authors: Ja June
authors: JJ
authors: Jang
authors: Chul Woo
authors: CW
authors: Kim
authors: Sang Ho
authors: SH
authors: Kim
authors: Jung Young
authors: JY
authors: Lee
authors: Nam Jin
authors: NJ
authors: Yoo
authors: Sug Hyung
authors: SH
authors: Lee
mesh_terms: D000483:Alleles; D001483:Base Sequence; D053455:Caspase 10; D020169:Caspases / Q000235:genetics*; D017931:DNA Primers; D005091:Exons; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000201:enzymology / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D017931:DNA Primers; D011994:Recombinant Proteins; D053455:Caspase 10; D020169:Caspases; C105036:interleukin 1beta-converting enzyme 2; C506438:CASP10 protein, human