Mutations in Bcl10 are very rare in colorectal cancer

Stone, Joanne; Rowan, Andrew; Tomlinson, Ian; Houlston, Richard S.

doi:10.1038/sj.bjc.6690562

Cited by 23 publications

(18 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[15][16][17][18][19] In particular, in B cell neoplasms BCL10 mutations were observed as very rare events. [20][21][22] Some of the discrepancies between the initial reports of mutations in MALT lymphoma 10,11 and the subsequent data [15][16][17][18][19][20][21][22] were ascribed to post-transcriptional modification resulting in sequence alterations detectable on the Leukemia cDNA but not on the genomic DNA level. 23,24 However, this mechanism of BCL10 disruption was not observed in our study based on RNA analysis.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2000

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

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

et al. 2000

View full text Add to dashboard Cite

show abstract

“…14) However, these findings have been challenged by a series of recent studies raising questions regarding the pathological role of BCL10 as a tumor suppressor gene in various human tumors. [18][19][20][21][22][23] The present study aimed to investigate the actual frequency and spectrum of mutations of the BCL10 gene in various primary B-cell NHLs. Our results suggest that nucleotide changes at codon 162 of BCL10 may occur in a small subset of DLBL and FCL.…”

Section: Discussionmentioning

confidence: 99%

“…14) However, several recent studies have reported that BCL10 mutations are very rare in various human tumors, thus raising questions regarding the pathological role of the BCL10 gene in these tumors. [18][19][20][21][22][23] Furthermore, the actual frequency and spectrum of the involvement of the BCL10 mutations in Bcell non-Hodgkin's lymphomas (NHL) remain to be established.…”

mentioning

confidence: 99%

Infrequent BCL10 Mutations in B‐Cell Non‐Hodgkin's Lymphomas

Takahashi

Hosokawa

Suzuki

et al. 1999

Japanese Journal of Cancer Research

View full text Add to dashboard Cite

The BCL10 gene was recently isolated from the breakpoint region of t(1;14)(p22;q32) in mucosaassociated lymphoid tissue (MALT) lymphomas. Somatic mutations of BCL10 were found in not only t(1;14)-bearing MALT lymphomas, but also a wide range of other tumors. To clarify the actual frequency and spectrum of BCL10 mutations in primary B-cell non-Hodgkin's lymphomas (NHL), we examined a total of 139 NHL cases comprising 25 with MALT lymphomas, 54 with follicular B-cell lymphomas (FCL), and 60 with diffuse large B-cell lymphomas (DLBL). Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and sequencing analyses led to the identification of four nucleotide changes in FCL and one in DLBL. In contrast, no BCL10 mutations were found in our series of MALT lymphomas. While screening for mutations, we also found three polymorphic sequence variants at codons 5 and 213 and in intron 1 of the BCL10 gene. Our results strongly suggest that somatic mutations of BCL10, if they occur at all, are rare in B-cell NHLs and do not commonly contribute to their molecular pathogenesis. Key words: Chromosome translocation -Apoptosis -SSCP -Malignant lymphomaRecurrent chromosomal translocations are well recognized and have been extensively characterized in nodal Bcell lymphomas.1, 2) These translocations were found to involve and deregulate an impressive list of proto-oncogenes including BCL1, BCL2, BCL6, and c-myc. In contrast, data on the molecular genetic mechanisms underlying the pathogenesis of marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type are only now beginning to emerge. Recurrent abnormalities found in MALT lymphomas include trisomies of chromosomes 3, 7, 12, and 18, the t(1;14)(p22;q32), and the t(11;18)(q21;q21).3-9) The t(11;18) translocation is reported to be one of the most frequent and specific chromosomal translocations in MALT lymphomas 7-9) and a novel gene, named MALT1 or MLT, has recently been cloned by ourselves and others from the breakpoint of the t(11;18). [10][11][12] On the other hand, the frequency of the t(1;14) translocation is relatively low and this translocation appears to be characteristic of aggressive MALT lymphomas. 13)The BCL10 gene has been isolated from the breakpoint region of the t(1;14) in MALT lymphomas.14, 15) BCL10, also called CIPER or CARMEN, was found to be a cellular homolog of the equine herpesvirus-2 E10 gene: both contain an amino-terminal caspase recruitment domain (CARD), which is homologous to that found in several apoptotic molecules.14-17) By analogy to BCL2 involvement in follicular B-cell lymphomas (FCL), BCL10 was expected to be anti-apoptotic. In functional assays, however, wild-type BCL10 turned out to be pro-apoptotic. It is noteworthy that BCL10 in t(1;14)-bearing MALT lymphomas exhibited a variety of truncating mutations.14, 15) As expected, the truncated BCL10 was shown to lose its proapoptotic action and display a gain-of-function transforming activity, so that it is conceivable that such mutations may confer a surviva...

show abstract

“…Cependant, la présence d'ADNc alté-rés de bcl10 dans de nombreuses autres tumeurs lymphoïdes ou solides (mésothéliome, tératocarcinome)* révélée par l'équipe de M. Dyer jetait un trouble [1]. De nombreuses équipes cherchèrent alors à préciser ces résultats en étudiant la structure génomique de bcl10 dans diverses tumeurs [10][11][12][13][14]. En fait, les altérations somatiques de bcl10 dans les tumeurs sont très rares (même si les techniques de SSCP utilisées ne mettent théori-quement pas à l'abri de résultats faussement négatifs lorsque les cellules porteuses de l'anomalie recherchée sont diluées dans l'échantillon étu-NOUVELLES médecine/sciences 1999 ; 15 : 1469-71 …”

Section: Bcl10 : Rôle Ambigu Dans La Cascade Apoptotique Et La Tumoriunclassified

BCL10 : rôle ambigu dans la cascade apoptotique et la tumorigenèse.

Salles¹

1999

Med Sci (Paris)

View full text Add to dashboard Cite

Mutations in Bcl10 are very rare in colorectal cancer

Cited by 23 publications

References 5 publications

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

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

Infrequent BCL10 Mutations in B‐Cell Non‐Hodgkin's Lymphomas

BCL10 : rôle ambigu dans la cascade apoptotique et la tumorigenèse.

Contact Info

Product

Resources

About