Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma.

Authors: Kaiser, MF  Johnson, DC  Wu, P  Walker, BA  Brioli, A  Mirabella, F  Wardell, CP  Melchor, L  Davies, FE  Morgan, GJ 
Citation: Kaiser MF, etal., Blood. 2013 Jul 11;122(2):219-26. doi: 10.1182/blood-2013-03-487884. Epub 2013 May 22.
Pubmed: (View Article at PubMed) PMID:23699600
DOI: Full-text: DOI:10.1182/blood-2013-03-487884

Outcome in multiple myeloma is highly variable and a better understanding of the factors that influence disease biology is essential to understand and predict behavior in individual patients. In the present study, we analyzed combined genomewide DNA methylation and gene expression data of patients treated in the Medical Research Council Myeloma IX trial. We used these data to identify epigenetically repressed tumor suppressor genes with prognostic relevance in myeloma. We identified 195 genes with changes in methylation status that were significantly associated with prognosis. Combining DNA methylation and gene expression data led to the identification of the epigenetically regulated tumor modulating genes GPX3, RBP1, SPARC, and TGFBI. Hypermethylation of these genes was associated with significantly shorter overall survival, independent of age, International Staging System score, and adverse cytogenetics. The 4 differentially methylated and expressed genes are known to mediate important tumor suppressive functions including response to chemotherapy (TGFBI), interaction with the microenvironment (SPARC), retinoic acid signaling (RBP1), and the response to oxidative stress (GPX3), which could explain the prognostic impact of their differential methylation. Assessment of the DNA methylation status of the identified genes could contribute to the molecular characterization of myeloma, which is prerequisite for an individualized treatment approach.

Annotation

Disease Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 11073605
Created: 2016-04-29
Species: All species
Last Modified: 2016-04-29
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.