Mutation ofBAX occurs infrequently in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas

Gaïdano, Gianluca; Vivenza, Daniela; Forconi, Francesco; Capello, Daniela; Gloghini, Annunziata; Bhatia, Kishor; Gutiérrez, Marina; Gallicchio, Margherita; Avanzi, Gian Carlo; Fassone, Lucia; Ariatti, Cristiano; Buonaiuto, Daniela; Cingolani, Antonella; Saglio, Giuseppe; Tirelli, Umberto; Larocca, Luigi Maria; Dalla‐Favera, Riccardo; Carbone, Antonino

doi:10.1002/(sici)1098-2264(200002)27:2<177::aid-gcc9>3.0.co;2-o

Cited by 40 publications

(49 citation statements)

References 32 publications

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“…This is supported by in vitro studies showing that mutations may alter the transcriptional activity of bcl-6. 29,30,44 The level of expression of bcl-6 in these cases did not differ substantially from expression in non-mutated cases, where bcl-6 is mainly expressed in the germinal center, and at lower intensity in marginal zone cells. In this study, mutations in the bcl-6 gene have been found in benign germinal centers as well as marginal zone cells of normal spleen.…”

Section: Discussionmentioning

confidence: 81%

“…29,30 Different studies suggest that bcl-6 and IgV H mutations are produced through the same mechanism, in the same cell compartments, 21,22 and that the difference in the mutability of the IgV H and bcl-6 genes may be attributable to differences in transcription rates or qualitative differences in control elements. 22 Thus essentially the lymphoma types in which IgV H mutations are detected simultaneously display bcl-6 mutations, albeit at a lower frequency.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22][23] These mutations are found independently of bcl-6 rearrangement in DLBCL and FL. 29,30 Recent studies indicate that these mutations accumulating in the regulatory region of the bcl-6 gene may play a role in lymphoma progression and in the transformation of FL to more aggressive large cell lymphoma. 31,32 …”

Section: Introductionmentioning

confidence: 99%

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Molecular heterogeneity of splenic marginal zone lymphomas: analysis of mutations in the 5′ non-coding region of the bcl-6 gene

Mollejo

Villuendas

et al. 2001

Leukemia

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Splenic marginal zone lymphoma (SMZL) has been recognized as a distinctive type of small B cell lymphoma, and defined on the basis of its morphological, phenotypic, clinical and molecular characteristics. In spite of this, the borders of the entity, the homogeneity of the cases and the presumably cell origin of SMZL remain controversial issues. The frequency of mutation in the 5′ non-coding region of the bcl-6 gene has been used as a marker of germinal center derivation, which may be used to establish the molecular heterogeneity of different non-Hodgkin lymphoma (

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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Molecular heterogeneity of splenic marginal zone lymphomas: analysis of mutations in the 5′ non-coding region of the bcl-6 gene

Mollejo

Villuendas

et al. 2001

Leukemia

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“…These mutations are found in cases displaying either normal or rearranged bcl-6 alleles, indicating their independence of chromosomal rearrangement. The sequences affected by these mutations are adjacent to the bcl-6 promotor region and overlap with the major cluster of chromosomal breakpoint (15). The mutation frequency is more than 70% in DLCL, which is much higher than that of rearrangement (7), and the high frequency, tumor specificity and location in the proximity of bcl-6 regulatory regions of these mutations suggest that these genetic lesions may play a role in lymphomagenesis (16).…”

Section: Discussionmentioning

confidence: 97%

“…Because the bcl-6 expression is more frequently observed than anticipated by cytogenetic and Southern blot analysis, other mechanisms of gene activation such as point mutation or deletion are considered to be involved (12,13,14). Recent studies revealed frequent mutation of the bcl-6 gene in the 5' noncoding region (15,16), but not in the coding region (17) in malignant lymphomas. Bcl-6 mutations are also frequently found in the neoplastic counterparts of germinal center cells, including DLCL and FL, as well as the postgerminal center origin tumor (multiple myeloma) (7,18).…”

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confidence: 99%

Mutational Analysis of the 5′ Noncoding Region of the Bcl-6 Gene in Primary Gastric Lymphomas

Yang

Ree

2001

Modern Pathology

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Bcl-6 mRNA and protein are frequently expressed in the transformed counterparts of the germinal center B-cells, diffuse large B-cell lymphoma and follicular lymphoma, irrespective of the gene rearrangements. Most of the primary gastric lymphomas are thought to be of mucosa-associated lymphoid tissue (MALT) origin, and neither bcl-6 gene rearrangement nor protein expression is found in low-grade gastric lymphomas of the MALT type as in normal marginal zone cells. However, bcl-6 protein expression was identified in highgrade gastric lymphomas, suggesting its role in high-grade transformation. In this study, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis for bcl-6 primer was performed in order to ascertain the molecular mechanisms of bcl-6 protein expression in primary gastric lymphomas. A total 31 cases of gastric lymphoma were classified into low-grade gastric lymphomas of MALT type (n ‫؍‬ 13), high-grade gastric lymphomas of MALT type (n ‫؍‬ 6) and gastric diffuse large B-cell lymphomas (n ‫؍‬ 12). Bcl-6 mutations were observed in 11 of 13 (84.6%) low-grade gastric lymphomas of the MALT type and in 8 of 12 (66.7%) diffuse large B-cell gastric lymphomas. In 6 cases of the high-grade gastric lymphomas of the MALT type, both the low-and high-grade components demonstrated the same frequency (3/6, 50%) of mutations. The tissue obtained from the marginal zone of Peyer's patch by microdissection technique revealed no bcl-6 mutations by the PCR-SSCP analysis. These findings suggest that the acquisition process of bcl-6 mutations by the marginal zone cells may be involved in the lymphomagenesis of the stomach, but our data does not explain the reason why bcl-6 protein is expressed only in high-grade gastric lymphomas.

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Somatic hypermutation and B-cell malignancies

Spencer

Dunn-Walters

1999

J. Pathol.

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Mutation ofBAX occurs infrequently in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas

Cited by 40 publications

References 32 publications

Molecular heterogeneity of splenic marginal zone lymphomas: analysis of mutations in the 5′ non-coding region of the bcl-6 gene

Molecular heterogeneity of splenic marginal zone lymphomas: analysis of mutations in the 5′ non-coding region of the bcl-6 gene

Mutational Analysis of the 5′ Noncoding Region of the Bcl-6 Gene in Primary Gastric Lymphomas

Somatic hypermutation and B-cell malignancies

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