Kaiser, M. F., Johnson, D. C., Wu, P., Walker, B. A., Brioli, A., Mirabella, F., Wardell, C. P., Melchor, L., Davies, F. E., Morgan, G. J. (2013) Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma. BLOOD, 122 (2). pp. 219-226. ISSN 0006-4971

Full text not available from this repository.

Abstract

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.

Item Type:	Article
Authors (ICR Faculty only):	Morgan, Gareth and Davies, Faith
All Authors:	Kaiser, M. F., Johnson, D. C., Wu, P., Walker, B. A., Brioli, A., Mirabella, F., Wardell, C. P., Melchor, L., Davies, F. E., Morgan, G. J.
Additional Information:	Kaiser, Martin F. Johnson, David C. Wu, Ping Walker, Brian A. Brioli, Annamaria Mirabella, Fabio Wardell, Christopher P. Melchor, Lorenzo Davies, Faith E. Morgan, Gareth J.
Research teams:	ICR divisions > Clinical Studies > Molecular Haematology (including Cytogenetics Group and Cell Markers) ICR divisions > Molecular Pathology > Molecular Haematology (including Cytogenetics Group and Cell Markers) Closed research groups > Myeloma Targeted Treatment
Depositing User:	Users 11 not found.
Date Deposited:	02 Sep 2013 11:23
Last Modified:	16 Nov 2015 15:33
URI:	http://publications.icr.ac.uk/id/eprint/12683

Actions (login required)

View Item