Inactivating mutations of CASP10 gene in non-Hodgkin lymphomas.
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.
Shin
Min Sun
MS
Department of PathologyCollege of Medicine, The Catholic University of Korea, Seoul, Korea.
Kim
Hong Sug
HS
Kang
Chang Suk
CS
Park
Won Sang
WS
Kim
Su Young
SY
Lee
Shi Nae
SN
Lee
Jong Heun
JH
Park
Jik Young
JY
Jang
Ja June
JJ
Kim
Chul Woo
CW
Kim
Sang Ho
SH
Lee
Jung Young
JY
Yoo
Nam Jin
NJ
Lee
Sug Hyung
SH
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
D017931:DNA Primers; D011994:Recombinant Proteins; D053455:Caspase 10; D020169:Caspases; C105036:interleukin 1beta-converting enzyme 2; C506438:CASP10 protein, human