DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage.

DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage. Research Abstract Details 

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DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage. Abstract Text:

Ian M Smith,Wojciech K Mydlarz,Suhail K Mithani,Joseph A Califano,

Epigenetic changes have been implicated in the pathogenesis of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Prior efforts have primarily examined regional promoter hypermethylation as a silencer of tumor suppressor gene expression. To analyze the global state of methylation in the HNSCC genome, we utilize pyrosequencing of repetitive elements (LINEs) to compare the state of global methylation in HNSCC to normal aerodigestive mucosa. 137 samples (119 HNSCC tumors and 18 normal mucosal tissues) were digested to extract DNA and subjected to bisulfite treatment. Treated DNA was amplified using PCR primers for the repetitive LINEs sequence and produced a heterogeneous sample of products, from many genomic loci. These products were pyrosequenced to quantitatively evaluate their global genomic methylation status. HNSCC specimens showed global hypomethylation, with a mean level of genomic methylation of 46.8% methylated with a standard deviation of 9.0. Conversely, the normal upper airway mucosa had a global methylation level of 54.0 and a standard deviation of 4.6 (Mann-Whitney p value < 0.001). The tumor specimens also showed an increasing degree of hypomethylation associated with advanced tumor stage (ANOVA p-value of 0.003). About 67% of HNSCC's are globally hypomethylated when evaluated against the minimum level of methylation in the normal mucosal specimens. Degree of global hypomethylation was associated with smoking history, alcohol use and stage in univariate analysis (p-value 0.02), however, only HNSCC diagnosis remained significant on multivariate analysis. Despite the presence of regional promoter hypermethylation, HNSCC demonstrates global genomic hypomethylation. The effects of stage, alcohol use and smoking on global hypomethylation were not independently significant.

DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage. Publishing Authors By Initials

IM Smith,WK Mydlarz,SK Mithani,JA Califano,

For similar behavior and behavior mechanisms: behavior: habits: smoking research abstracts see: behavior and behavior mechanisms: behavior: habits: smoking research

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DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: International journal of cancer. Journal internati

VOLUME: 121

Page Numbers: 1724-8

Journal Abbreviation: Int. J. Cancer

ISSN: 0020-7136

DAY: 15

MONTH: Oct

YEAR: 2007

DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 42124

DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage. Keywords Mesh Terms:

KEYWORDS: Smoking

MESH TERMS: adverse effects

Chemical & Substance for Abstract: DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage. Information

Substance Name: DNA Primers

Registry Number: 0

Grant and Affiliation Information for DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage.

AFFILIATION: Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287-0910, USA.

Country: United States

AGENCY: United States NCI

GRANT: 5P50CA096784-05

ACRONYM: CA

MEDLINETA: Int J Cancer

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