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. 2014 Aug 20;6(1):16.
doi: 10.1186/1868-7083-6-16. eCollection 2014.

Methylation analysis of the phosphates and tensin homologue on chromosome 10 gene (PTEN) in multiple myeloma

Giovanna Piras  1 , Maria Monne  1 , Angelo D Palmas  1 , Anna Calvisi  1 , Rosanna Asproni  1 , Francesco Vacca  1 , Laura Pilo  1 , Attilio Gabbas  1 , Giancarlo Latte  1
Affiliations

Methylation analysis of the phosphates and tensin homologue on chromosome 10 gene (PTEN) in multiple myeloma

Giovanna Piras et al. Clin Epigenetics. .

Abstract

Background: Aberrant DNA methylation of promoter region CpG islands is an alternative mechanism that leads to genetic defects in the inactivation of tumor suppressor genes during myelomagenesis. The aim of this study was to examine the promoter methylation status of the phosphates and tensin homologue on chromosome 10 (PTEN) gene in a cohort of multiple myeloma patients.

Findings: The PTEN gene was hypermethylated in 7 out of 58 (12%) primary myeloma samples. The correlation between functional inactivation and PTEN mRNA levels was not statistically significant. The multiple myeloma subgroup with an aberrant PTEN status had a prevalence of the component IgG, Salmon Durie stage I, lower lactate dehydrogenase levels, intermediate-standard cytogenetic risk and longer overall survival with the respect to the unmethylated subgroup.

Conclusions: This is the first report demonstrating the presence of PTEN promoter hypermethylation in multiple myeloma.

Keywords: Akt pathway; PTEN; Promoter hypermethylation; multiple myeloma.

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Figures

Figure 1
Figure 1
PTENgene hypermethylation analysis in multiple myeloma patients. (A) Representative methylation specific polymerase chain reaction (MSP) results for PTEN in patient samples. The positive and negative controls showed the expected MSP results with normal DNA showing positive U-MSP but negative M-MSP amplification, and conversely, the methylated control DNA showing negative U-MSP but positive M-MSP amplification. (B) Kaplan-Meyer survival function of multiple myeloma (MM) patients with or without PTEN promoter hypermethylation, P value = 0.53. (C) Heatmap of the PTEN analyses showing methylation status, quantitative reverse transcriptase PCR (qRT-PCR) for PTEN relative gene expression and cytogenetic categories. MSP green, unmethylated; red, methylated; qRT-PCR: green, low expression; red, high expression and white, not determined. Cytogenetics: green, standard risk; red, high risk. (D) Box and whisker plot showed the PTEN expression in methylated and unmethylated primary MM patients, P value = 0.87. (E) Survival curves of 58 patients with multiple myeloma according to SD staging (P = 0.053), and cytogenetic categories (P = 0.11).
See this image and copyright information in PMC

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