Correlation between BRAF mutation and promoter methylation of TIMP3, RARβ2 and RASSF1A in thyroid cancer

Mariana Brait Rodrigues De Oliveira, Myriam Loyo, Eli Rosenbaum, Kimberly Ostrow, Alina Markova, Silvana Papagerakis, Marianna Zahurak, Steven N. Goodman, Martha Zeiger, David Sidransky, Christopher B Umbricht, Mohammad Hoque

Research output: Contribution to journalArticle

Abstract

Our aim was to comprehensively analyze promoter hypermethylation of a panel of novel and known methylation markers for thyroid neoplasms and to establish their relationship with BRAF mutation and clinicopathologic parameters of thyroid cancer. A cohort of thyroid tumors, consisting of 44 cancers and 44 benign thyroid lesions, as well as 15 samples of adjacent normal thyroid tissue, was evaluated for BRAF mutation and promoter hypermethylation. Genes for quantitative methylation specific PC R (QMSP) were selected by a candidate gene approach. Twenty-two genes were tested: TSHR, RASSF1A, RARβ2, DAPK, hMLH1, ATM, S100, p16, CTNNB1, GSTP1, CALCA, TIMP3, TGFβR2, THBS1, MINT1, CTNNB1, MT1G, PAK3, NISCH, DCC, AIM1 and KIF1A. The PC R-based "mutector assay" was used to detect BRAF mutation. All p values reported are two sided. Considerable overlap was seen in the methylation markers among the different tissue groups. Significantly higher methylation frequency and level were observed for KIF1A and RARβ2 in cancer samples compared with benign tumors. A negative correlation between BRAF mutation and RASSF1A methylation, and a positive correlation with RARβ2 methylation were observed in accordance with previous results. In addition, positive correlation with TIMP3 and a marginal correlation with DCC methylation were observed. The present study constitutes a comprehensive promoter methylation profile of thyroid neoplasia and shows that results must be analyzed in a tissue-specific manner to identify clinically useful methylation markers. Integration of genetic and epigenetic changes in thyroid cancer will help identify relevant biologic pathways that drive its development.

Original languageEnglish (US)
Pages (from-to)710-719
Number of pages10
JournalEpigenetics
Volume7
Issue number7
DOIs
StatePublished - Jul 2012

Fingerprint

Thyroid Neoplasms
Methylation
Mutation
Thyroid Gland
Neoplasms
Genes
Epigenomics

Keywords

  • Biomarkers
  • BRAF
  • Hypermethylation
  • RARβ2
  • RASSF1A
  • Thyroid cancer
  • Thyroid tissue
  • TIMP3

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Correlation between BRAF mutation and promoter methylation of TIMP3, RARβ2 and RASSF1A in thyroid cancer. / Brait Rodrigues De Oliveira, Mariana; Loyo, Myriam; Rosenbaum, Eli; Ostrow, Kimberly; Markova, Alina; Papagerakis, Silvana; Zahurak, Marianna; Goodman, Steven N.; Zeiger, Martha; Sidransky, David; Umbricht, Christopher B; Hoque, Mohammad.

In: Epigenetics, Vol. 7, No. 7, 07.2012, p. 710-719.

Research output: Contribution to journalArticle

Brait Rodrigues De Oliveira, Mariana ; Loyo, Myriam ; Rosenbaum, Eli ; Ostrow, Kimberly ; Markova, Alina ; Papagerakis, Silvana ; Zahurak, Marianna ; Goodman, Steven N. ; Zeiger, Martha ; Sidransky, David ; Umbricht, Christopher B ; Hoque, Mohammad. / Correlation between BRAF mutation and promoter methylation of TIMP3, RARβ2 and RASSF1A in thyroid cancer. In: Epigenetics. 2012 ; Vol. 7, No. 7. pp. 710-719.
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AU - Ostrow, Kimberly

AU - Markova, Alina

AU - Papagerakis, Silvana

AU - Zahurak, Marianna

AU - Goodman, Steven N.

AU - Zeiger, Martha

AU - Sidransky, David

AU - Umbricht, Christopher B

AU - Hoque, Mohammad

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