BCL10 is not the gene inactivated by mutation in the 1p22 deletion region in mantle cell lymphoma.
The BCL10 gene has recently been cloned from the 1p22 breakpoint of the translocation t(1 ;14)(p22;q32) observed in mucosa-associated lymphoid tissue (MALT) lymphoma. BCL10 was shown to be a proapoptotic-signaling gene encoding a protein that contains an amino-terminal caspase recruitment domain (CARD). Mutations within the BCL10 coding region resulting in truncated BCL10 proteins with loss of their proapoptotic function and preservation of their NF-kappaB activating function were detected in MALT lymphoma. Based on these findings it was proposed that BCL10 might have tumor suppressor function. Deletions involving 1p22 are commonly observed in mantle cell lymphoma (MCL). To investigate its role in MCL we have analyzed a series of 15 MCL for deletion and mutation of BCL10. Monoallelic 1p22 deletions were detected by fluorescence in situ hybridization in five of the 15 cases and were shown to affect BCL10 in all cases. BCL10 was screened for mutations by DNA sequencing of RT-PCR amplified transcripts. In none of the 15 MCL cases studied were mutations found in the BCL10 coding region. A previously reported polymorphism exhibiting a silent 24C > G substitution was found in eight MCL cases and in four healthy probands. A missense mutation 13G >T resulting in a substitution of a serine by an alanine was seen in one of the controls. Our results strongly suggest that BCL10 is not the candidate tumor suppressor gene inactivated by deletion or mutation in band 1p22 in MCL.
Bullinger
L
L
Abteilung Innere Medizin III, University of Ulm, Germany.
Leupolt
E
E
Schaffner
C
C
Mertens
D
D
Bentz
M
M
Lichter
P
P
Döhner
H
H
Stilgenbauer
S
S
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D017931:DNA Primers; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000235:genetics*; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D017931:DNA Primers; D009363:Neoplasm Proteins