BCL10 is not the gene inactivated by mutation in the 1p22 deletion region in mantle cell lymphoma

Abstract

The BCL10 gene has recently been cloned from the 1p22 breakpoint of the translocation t(1;14)(p22;q32) observed in mucosaassociated 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-B 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 Ͼ G substitution was found in eight MCL cases and in four healthy probands. A missense mutation 13G ϾT 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.

BCL10 in malignant lymphomas – an evaluation using fluorescence in situ hybridization

“…Overall, our FISH analysis demonstrated translocations involving BCL10 to be uncommon (1/22) and limited to the MALT subtype. The single translocation involving BCL10 did not result in disruption of the gene, which would support the observation of Bullinger et al 18. and suggest that this is not necessarily the gene inactivated at 1p22.…”

Genomic aberrations in mantle cell lymphoma detected by interphase fluorescence in situ hybridization. Incidence and clinicopathological correlations

“…For example, in the commonly deleted region 1p21-p22 mutation analyses failed to identify mutations in the coding region of BCL10, a likely candidate in this region. 33 However, the recent identification of miRNA-137 in the commonly deleted 1p region suggests that deregulation and/or mutation of miRNA might play a role in MCL in analogy to cases of chronic lymphocytic leukemia (CLL) with deletions of 13q14. 34 While additional, miRNA might be involved in the pathogenesis of MCL parallel analysis of genomic aberrations and mRNA as well as miRNA expression levels will help to further narrow down the number of potential candidate genes.…”

Quantitative microsatellite analysis to delineate the commonly deleted region 1p22.3 in mantle cell lymphomas

“…The BCL10 locus (AL590113) is deleted in 34/63 and the CLCA2 locus (AL122002) in 36/63 cases. Previously carried out mutation and methylation analyses showed no evidence that BCL10 is the tumor suppressor gene involved in MCL pathogenesis (Bullinger et al, 2000;Steinemann et al, 2000). Haploinsufficiency, however, cannot be ruled out.…”

“…The common region of deletion comprises the candidate tumor suppressor BCL10 gene, which was first identified as a mutated gene in MALT lymphomas (Willis et al, 1999;Zhang et al, 1999). Mutation and methylation analyses yet showed no evidence that BCL10 is the tumor suppressor involved in the pathogenesis of MCL (Bullinger et al, 2000;Steinemann et al, 2000). However, haploinsufficiency cannot be ruled out.…”