Mutational analysis of CASP10 gene in acute leukaemias and multiple myelomas.
AIMS: Deregulation of apoptosis is one of the hallmarks of cancers. Inactivation of cancer cell apoptosis by somatic mutations has been reported in several cancers. Caspase-10 activation is important in the initiation phase of apoptosis. The aim of this study was to explore whether CASP10 gene that encodes caspase-10 is somatically mutated in acute adulthood leukaemias and multiple myelomas (MMs). METHODS: We analysed the entire coding region and all splice sites of CASP10 gene for the detection of somatic mutations in 60 acute leukaemias (25 acute myelogenous leukaemias, 35 acute lymphoblastic leukaemias) and 22 multiple myelomas by a single-strand conformation polymorphism assay. RESULTS: Overall, we found two CASP10 mutations in the cancers (2/82; 2.4%). One mutation [c.854T>C (pLeu285Pro)] was detected in a T-acute lymphoblastic leukaemia (T-ALL) (1/13 T-ALL; 7.7%). The other mutation [c.61C>T (p.Arg21Cys)] was found in an MM (1/22 MM; 4.5%). The mutations were identified in the coding regions of the death effector domain (p.Arg21Cys) and the p17 large protease subunit (pLeu285Pro). We observed both of the T-ALL and the MM with the CASP10 mutations well expressed the mutant CAS10 at mRNA level. CONCLUSION: Although our data indicate that somatic mutation of CASP10 is not common in T-ALL and MM, the data suggest a possibility that CASP10 mutation might contribute to the pathogenesis of factions of T-ALL and MM.