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: Min Sun Shin, Hong Sug Kim, Chang Suk Kang, Won Sang Park, Su Young Kim, Shi Nae Lee, Jong Heun Lee, Jik Young Park, Ja June Jang, Chul Woo Kim, Sang Ho Kim, Jung Young Lee, Nam Jin Yoo, Sug Hyung Lee
• Journal: Blood (Blood) Vol. 99 Issue 11 Pg. 4094-9 (Jun 01 2002) ISSN: 0006-4971 [Print] United States
• PMID: 12010812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Recombinant Proteins
• Caspase 10
• Caspases
• interleukin 1beta-converting enzyme 2
• CASP10 protein, human

Topics

• Alleles
• Base Sequence
• Caspase 10
• Caspases (genetics)
• DNA Primers
• Exons
• Humans
• Lymphoma, Non-Hodgkin (enzymology, genetics)
• Mutagenesis, Site-Directed
• Mutation
• Polymorphism, Single-Stranded Conformational
• Recombinant Proteins (metabolism)