Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors

Megan L. Durr, Wojciech Mydlarz, Chunbo Shao, Marianna L. Zahurak, Alice Y. Chuang, Mohammad Hoque, William H. Westra, Nanette J. Liegeois, Joseph A. Califano, David Sidransky, Patrick K. Ha

Research output: Contribution to journalArticle

Abstract

Background: Methylation profiling of tumor suppressor gene (TSGs) promoters is quickly becoming a powerful diagnostic tool for the early detection, prognosis, and even prediction of clinical response to treatment. Few studies address this in salivary gland tumors (SGTs); hence the promoter methylation profile of various TSGs was quantitatively assessed in primary SGT tissue to determine if tumor-specific alterations could be detected. Methodology: DNA isolated from 78 tumor and 17 normal parotid gland specimens was assayed for promoter methylation status of 19 TSGs by fluorescence-based, quantitative methylation-specific PCR (qMSP). The data were utilized in a binary fashion as well as quantitatively (using a methylation quotient) allowing for better profiling and interpretation of results. Principal Findings: The average number of methylation events across the studied genes was highest in salivary duct carcinoma (SDC), with a methylation value of 9.6, compared to the normal 4.5 (p≤0.0003). There was a variable frequency and individual methylation quotient detected, depending on the TSG and the tumor type. When comparing normal, benign, and malignant SGTs, there was a statistically significant trend for increasing methylation in APC, Mint 1, PGP9.5, RAR-β and Timp3. Conclusions/Significance: Screening promoter methylation profiles in SGTs showed considerable heterogeneity. The methylation status of certain markers was surprisingly high in even normal salivary tissue, confirming the need for such controls. Several TSGs were found to be associated with malignant SGTs, especially SDC. Further study is needed to evaluate the potential use of these associations in the detection, prognosis, and therapeutic outcome of these rare tumors.

Original languageEnglish (US)
Article numbere10828
JournalPLoS One
Volume5
Issue number5
DOIs
StatePublished - 2010

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Methylation
tumor suppressor genes
Glandular and Epithelial Neoplasms
salivary glands
Tumor Suppressor Genes
methylation
Tumors
Genes
promoter regions
neoplasms
Salivary Ducts
prognosis
carcinoma
Neoplasms
Ducts
Mentha
parotid gland
Carcinoma
mint
Mints

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors. / Durr, Megan L.; Mydlarz, Wojciech; Shao, Chunbo; Zahurak, Marianna L.; Chuang, Alice Y.; Hoque, Mohammad; Westra, William H.; Liegeois, Nanette J.; Califano, Joseph A.; Sidransky, David; Ha, Patrick K.

In: PLoS One, Vol. 5, No. 5, e10828, 2010.

Research output: Contribution to journalArticle

Durr, Megan L. ; Mydlarz, Wojciech ; Shao, Chunbo ; Zahurak, Marianna L. ; Chuang, Alice Y. ; Hoque, Mohammad ; Westra, William H. ; Liegeois, Nanette J. ; Califano, Joseph A. ; Sidransky, David ; Ha, Patrick K. / Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors. In: PLoS One. 2010 ; Vol. 5, No. 5.
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