Mutational analysis of CASP10 gene in acute leukaemias and multiple myelomas.
OBJECTIVE
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.


CONCLUSIONS
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.
Kim
Min Sung
MS
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Oh
Ji Eun
JE
Min
Chang Ki
CK
Lee
Seok
S
Chung
Nak Gyun
NG
Yoo
Nam Jin
NJ
Lee
Sug Hyung
SH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D053455:Caspase 10 / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics*; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D053455:Caspase 10; C506438:CASP10 protein, human