TGFbetaR2 aberrant methylation is a potential prognostic marker and therapeutic target in multiple myeloma.

Full Abstract

Multiple myeloma (MM) is an incurable hematological malignancy. Different studies demonstrated the occurrence of genetic and epigenetic alterations in MM. The aberrant methylation is one of the most frequent epigenetic alterations in human genome. This study evaluated the aberrant methylation status of 20 genes in 51 MM samples by quantitative methylation-specific PCR (QMSP) and compared the methylation profile with clinicopathological characteristics of the patients. The QMSP analyses showed that PTGS2 (100.0%), SFN (100.0%), CDKN2B (90.2%), CDH1 (88.2%), ESR1 (72.5%), HIC1 (70.5%), CCND2 (62.7%), DCC (45.1%) and TGFbetaR2 (39.2%) are frequently hypermethylated in MM while aberrant methylation of RARbeta (16.6%), MGMT (12.5%), AIM1 (12.5%), CDKN2A (8.3%), SOCS1 (8.3%), CCNA1 (8.3%) and THBS1 (4.1%) are rare events. There was no methylation of GSTP1, MINT31, p14ARF and RB1 in the samples tested. Hypermethylation of ESR1 was correlated positively with isotype IgA, while aberrant methylation of THBS1 correlated negatively with isotype IgG. Furthermore, hypermethylation of DCC and TGFbetaR2 were correlated with poor survival. The multivariate analysis showed ISS and TGFbetaR2 hypermethylation strongly correlated with poor outcome. This study represents the first quantitative evaluation of promoter methylation in MM and our data provide evidence that TGFbetaR2 hypermethylation, besides ISS, may be useful as prognostic indicator in this disease.

Author information

Author/s: de Carvalho, Fabrício (F); Colleoni, Gisele W B (GW); Almeida, Manuella S Sampaio (MS); Carvalho, André L (AL); Vettore, André L (AL);

Affiliation: Discipline of Hematology and Hemotherapy, Universidade Federal de São Paulo, UNIFESP/EPM, São Paulo, Brazil.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Oct; vol 125 (issue 8) : pp 1985-91

Dates: Created 2009/08/26; Completed 2009/09/21;

PMID: 19548309, status: MEDLINE (last retrieval date: 9/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Multiple Myeloma - genetics; therapy
Neoplasm Proteins - genetics
Polymerase Chain Reaction
Prognosis
Promoter Regions, Genetic - genetics
Protein-Serine-Threonine Kinases - genetics
Receptors, Transforming Growth Factor beta - genetics
Survival Rate

Associated Chemicals: Neoplasm Proteins (0) ; Receptors, Transforming Growth Factor beta (0) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; transforming growth factor-beta type II receptor (EC 2.7.11.30)

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