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International Journal of Hematology
Published in: International Journal of Hematology 1/2010

01-01-2010 | Original Article

Methylation status of nine tumor suppressor genes in multiple myeloma

Authors: Esteban Braggio, Angelo Maiolino, Maria E. Gouveia, Roberto Magalhães, João T. Souto Filho, Márcia Garnica, Marcio Nucci, Ilana Zalcberg Renault

Published in: International Journal of Hematology | Issue 1/2010

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Abstract

Aberrant methylation in promoter-associated CpG islands has been recognized as a major mechanism for tumor suppressor gene silencing in several malignancies. We determined the methylation status of nine tumor suppressor genes in 68 newly diagnosed MM patients by methylation-specific PCR. The frequency of promoter hypermethylation for individual genes was: CDH1, 50%; p16 INK4a , 42.8%; p15 INK4b , 16.2%; SHP1, 14.7%; ER and BNIP3, 13.2%; RARβ, 11.8%; DAPK 5.9%; and MGMT 0%. Overall, 79% of patients presented at least one hypermethylated gene. By univariate analysis, hypermethylation of DAPK (P < 0.001) and RARβ (P = 0.01) genes were identified as adverse prognostic features. Median OS of patients with hypermethylation in DAPK (4 months) and RARβ (34 months) was significantly lower than in patients without hypermethylation (median survival not reached), with values of P < 0.001 and P = 0.01, respectively. Our data suggest that DAPK and RARβ hypermethylation are adverse prognostic factors in MM. The relevance of these findings as poor prognosis indicators requires confirmation in a larger sample with longer follow-ups.
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Metadata
Title
Methylation status of nine tumor suppressor genes in multiple myeloma
Authors
Esteban Braggio
Angelo Maiolino
Maria E. Gouveia
Roberto Magalhães
João T. Souto Filho
Márcia Garnica
Marcio Nucci
Ilana Zalcberg Renault
Publication date
01-01-2010
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 1/2010
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-009-0459-2

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