Gain of chromosome region 18q21 including the MALT1 gene is associated with the activated B-cell-like gene expression subtype and increased BCL2 gene dosage and protein expression in diffuse large B-cell lymphoma

Publication

Gain of chromosome region 18q21 including the MALT1 gene is associated with the activated B-cell-like gene expression subtype and increased BCL2 gene dosage and protein expression in diffuse large B-cell lymphoma

Journal Paper/Review - May 1, 2008

Dierlamm Judith, Cogliatti Sergio B., Möller Peter, Schwaenen Carsten, Stein Harald, Löffler Markus, Spang Rainer, Trümper Lorenz, Siebert Reiner, Ott German, Haralambieva Eugenia, Murga Penas Eva M, Bentink Stefan, Wessendorf Swen, Berger Hilmar, Hummel Michael, Klapper Wolfram, Lenze Dido, Rosenwald Andreas, Deutsche Krebshilfe Network Project "Molecular Mechanisms in Malignant Lymphomas"

Citation

Dierlamm J, Cogliatti S, Möller P, Schwaenen C, Stein H, Löffler M, Spang R, Trümper L, Siebert R, Ott G, Haralambieva E, Murga Penas E, Bentink S, Wessendorf S, Berger H, Hummel M, Klapper W, Lenze D, Rosenwald A, Deutsche Krebshilfe Network Project "Molecular Mechanisms in Malignant Lymphomas". Gain of chromosome region 18q21 including the MALT1 gene is associated with the activated B-cell-like gene expression subtype and increased BCL2 gene dosage and protein expression in diffuse large B-cell lymphoma. Haematologica 2008; 93:688-96.

Type

Journal Paper/Review (English)

Journal

Haematologica 2008; 93

Publication Date

May 1, 2008

Issn Electronic

1592-8721

Pages

688-96

Brief description/objective

BACKGROUND: The aim of this study was to determine the impact of a gain of the MALT1 gene on gene expression and clinical parameters in diffuse large B-cell lymphoma. DESIGN AND METHODS: We analyzed 116 cases of diffuse large B-cell lymphoma by fluorescence in situ hybridization, array-based comparative genomic hybridization, and transcriptional profiling. RESULTS: A gain of 18q21 including MALT1 was detected in 44 cases (38%) and was accompanied by a gain of BCL2 in 43 cases. All cases with a 18q21/MALT1 gain showed BCL2 protein whereas 79% in the group without a 18q21/MALT1 gain did so (p<0.001). Cases with 18q21/MALT1 gain more frequently showed an activated B-cell-like (ABC) gene expression signature (65%) than a germinal center B-cell-like (GCB) one (23%) (p<0.001). Ninety-eight genes including MALT1, BCL2, and some selected nuclear factor-kappaB target genes were differentially expressed between the two genetic groups of diffuse large B-cell lymphoma. By global testing of each chromosome, we identified 33 genes, all located on chromosome 18q, which were differentially expressed between the two genetic groups independently of the ABC/GCB status. In multivariate analysis, the 18q21/MALT1 status represented an independent negative prognostic factor for overall survival (p=0.03). CONCLUSIONS: In diffuse large B-cell lymphoma, gain of 18q21 including MALT1 is significantly associated with differential expression of genes located on 18q, the ABC gene expression subtype, increased BCL2 gene and protein expression and might indicate an unfavorable prognosis.