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PMID: 20162572 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

KIF1A and EDNRB are differentially methylated in primary HNSCC and salivary rinses.

International journal of cancer ·Vol. 127 ·No. 10 ·2010-11-15 ·Pages 2351-9

Demokan S, Chang X, Chuang A, Mydlarz WK, Kaur J, Huang P, Khan Z, Khan T, Ostrow KL, Brait M, Hoque MO, Liegeois NJ, Sidransky D, Koch W, Califano JA

Abstract

Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. In this study, we aimed to evaluate to the utility of aberrant promoter hypermethylation for detection in a panel of 10 genes (KIF1A, EDNRB, CDH4, TERT, CD44, NISCH, PAK3, VGF, MAL and FKBP4) in head and neck squamous cell carcinoma (HNSCC) via a candidate gene approach. We investigated methylation of the gene promoters by bisulfite modification and quantitative methylation-specific PCR (Q-MSP) in a preliminary study of a limited cohort of salivary rinses from healthy subjects (n = 61) and patients with HNSCC (n = 33). The methylation status of 2 selected genes (EDNRB and KIF1A) were then analyzed in 15 normal mucosa samples from a healthy population, 101 HNSCC tumors and the corresponding salivary rinses from 71 out of the 101 HNSCC patients were collected before treatment. The promoter regions of CDH4, TERT, VGF, MAL, FKBP4, NISCH and PAK3 were methylated in normal salivary rinses while no methylation of CD44 was observed in either normal salivary rinses or tumor samples. However, KIF1A and EDNRB were methylated in 98 and 97% of primary HNSCC tissues respectively and were only methylated in 2 and 6.6% of normal salivary rinses. In addition, KIF1A and EDNRB were methylated in 38 and 67.6% of salivary rinses from HNSCC patients, respectively. Promoter hypermethylation of KIF1A and EDNRB is a frequent event in primary HNSCC, and these genes are preferentially methylated in salivary rinses from HNSCC patients. KIF1A and EDNRB are potential biomarkers for HNSCC detection.

MeSH Terms
Adult Aged Aged, 80 and over Carcinoma, Squamous Cell/genetics,pathology Case-Control Studies DNA Methylation Female Head and Neck Neoplasms/genetics,pathology Humans Kinesins/genetics Male Middle Aged Promoter Regions, Genetic Receptor, Endothelin B/genetics Saliva Salivary Glands/pathology Young Adult
Chemicals
KIF1A protein, human Receptor, Endothelin B Kinesins
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Demokan Semra
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Chang Xiaofei
Chuang Alice
Mydlarz Wojciech K
Kaur Jatinder
Huang Peng
Khan Zubair
Khan Tanbir
Ostrow Kimberly L
Brait Mariana
Hoque Mohammad O
Liegeois Nanette J
Sidransky David
Koch Wayne
Califano Joseph A
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Article Info
Journal
International journal of cancer
Abbr.
Int J Cancer
ISSN
1097-0215
Published
2010-11-15
Pages
2351-9
Language
English
Region
United States
NLM ID
0042124
PMCID
PMC2946472
Subset
IM
Grants
NCI NIH HHS · P20 CA118782 · United States
NCI NIH HHS · P20 CA118782-01 · United States
NCI NIH HHS · P50 CA096784 · United States
NCI NIH HHS · P50 CA96784 · United States
NCI NIH HHS · P50 CA096784-01 · United States
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