Pharmacologic unmasking of epigenetically silenced genes in breast cancer

Kimberly Ostrow, Hannah Lui Park, Mohammad Hoque, Myoung Sook Kim, Junwei Liu, Pedram Argani, William Westra, Wim Van Criekinge, David Sidransky

Research output: Contribution to journalArticle

Abstract

Purpose: Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of various cancers including breast cancer. Many epigenetically inactivated genes involved in breast cancer development remain to be identified. Therefore, in this study we used a pharmacologic unmasking approach in breast cancer cell lines with 5-aza-2′-deoxycytidine (5-aza-dC) followed by microarray expression analysis to identify epigenetically inactivated genes in breast cancer. Experimental Design: Breast cancer cell lines were treated with 5-aza-dC followed by micro-array analysis to identify epigenetically inactivated genes in breast cancer. We then used bisulfite DNA sequencing, conventional methylation-specific PGR, and quantitative fluorogenic real-time methylation-specific PGR to confirm cancer-specific methylation in novel genes. Results: Forty-nine genes were up-regulated in breast cancer cells lines after 5-aza-dC treatment, as determined by microarray analysis. Five genes (MAL, FKBP4, VGF, OGDHL, and KIF1A) showed cancer-specific methylation in breast tissues. Methylation of at least two was found at high frequency only in breast cancers (40 of 40) as compared with normal breast tissue (0 of 10; P <0,0001, Fisher's exact test). Conclusions: This study identified new cancer-specific methylated genes to help elucidate the biology of breast cancer and as candidate diagnostic markers for the disease.

Original languageEnglish (US)
Pages (from-to)1184-1191
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number4
DOIs
StatePublished - Feb 15 2009

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Breast Neoplasms
decitabine
Methylation
Genes
Microarray Analysis
Cell Line
Breast
Neoplasms
Tumor Suppressor Genes
DNA Sequence Analysis
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pharmacologic unmasking of epigenetically silenced genes in breast cancer. / Ostrow, Kimberly; Park, Hannah Lui; Hoque, Mohammad; Kim, Myoung Sook; Liu, Junwei; Argani, Pedram; Westra, William; Van Criekinge, Wim; Sidransky, David.

In: Clinical Cancer Research, Vol. 15, No. 4, 15.02.2009, p. 1184-1191.

Research output: Contribution to journalArticle

Ostrow, Kimberly ; Park, Hannah Lui ; Hoque, Mohammad ; Kim, Myoung Sook ; Liu, Junwei ; Argani, Pedram ; Westra, William ; Van Criekinge, Wim ; Sidransky, David. / Pharmacologic unmasking of epigenetically silenced genes in breast cancer. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 4. pp. 1184-1191.
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