Methylation status of nine tumor suppressor genes in multiple myeloma.

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%; RAR beta, 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 RAR beta (P = 0.01) genes were identified as adverse prognostic features. Median OS of patients with hypermethylation in DAPK (4 months) and RAR beta (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 RAR beta 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.

journal_name

Int J Hematol

authors

Braggio E,Maiolino A,Gouveia ME,Magalhães R,Souto Filho JT,Garnica M,Nucci M,Renault IZ

doi

10.1007/s12185-009-0459-2

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

87-96

issue

1

eissn

0925-5710

issn

1865-3774

journal_volume

91

pub_type

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