Dataset Information

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

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.

SUBMITTER: Demokan S

PROVIDER: S-EPMC2946472 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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

Demokan Semra S Chang Xiaofei X Chuang Alice A Mydlarz Wojciech K WK Kaur Jatinder J Huang Peng P Khan Zubair Z Khan Tanbir T Ostrow Kimberly L KL Brait Mariana M Hoque Mohammad O MO Liegeois Nanette J NJ Sidransky David D Koch Wayne W Califano Joseph A JA

International journal of cancer 20101101 10

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 prelimina ...[more]

PMID: 20162572

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Project description:Salivary rinses have been recently proposed as a valuable resource for the development of epigenetic biomarkers for detection and monitoring of head and neck squamous cell carcinoma (HNSCC). Both salivary rinses collected with and without an exfoliating brush from patients with HNSCC are used in detection of promoter hypermethylation, yet their correlation of promoter hypermethylation has not been evaluated. This study was to evaluate the concordance of promoter hypermethylation between salivary rinses collected with and without an exfoliating brush from patients with HNSCC. METHODOLGY: 57 paired salivary rinses collected with or without an exfoliating brush from identical HNSCC patients were evaluated for promoter hypermethylation status using Quantitative Methylation-Specific PCR. Target tumor suppressor gene promoter regions were selected based on our previous studies describing a panel for HNSCC screening and surveillance, including P16, CCNA1, DCC, TIMP3, MGMT, DAPK and MINT31.In salivary rinses collected with and without brush, frequent methylation was detected in P16 (8.8% vs. 5.2%), CCNA1 (26.3% vs. 22.8%), DCC (33.3% vs. 29.8%), TIMP3 (31.6% vs. 36.8%), MGMT (29.8% vs. 38.6%), DAPK (14.0% vs. 19.2%), and MINT31 (10.5% vs. 8.8%). Spearman's rank correlation coefficient showed a positive correlation between salivary rinses collected with and without brush for P16 (? = 0.79), CCNA1 (? = 0.61), DCC (? = 0.58), TIMP3 (? = 0.10), MGMT (? = 0.70), DAPK (? = 0.51) and MINT31 (? = 0.72) (P<0.01). The percent agreement of promoter methylation between salivary rinses with brush and without brush were 96.5% for P16, 82.5% for CCNA1, 78.9% for DCC, 59.7% for TIMP3, 84.2% for MGMT, 84.2% for DAPK, and 94.7% for MINT31.Our study demonstrated strong correlations of gene promoter hypermethylation between salivary rinses collected with and without an exfoliating brush. Salivary rinse collection without using an exfoliating brush may offer a cost effective, rapid, non-invasive, and reliable means for development of epigenetic salivary rinse biomarkers.

Project description:BackgroundGrowing evidence shows that epigenetic modifications play a role in Alzheimer's disease (AD). We performed an epigenome-wide association study (EWAS) to evaluate the DNA methylation differences using postmortem superior temporal gyrus (STG) and inferior frontal gyrus (IFG) samples.ResultsSamples from 72 AD patients and 62 age-matched cognitively normal controls were assayed using Illumina© Infinium MethylationEPIC BeadChip. Five and 14 differentially methylated positions (DMPs) associated with pathology (i.e., Braak stage) with p value less than Bonferroni correction threshold of 6.79 × 10-8 in the STG and IFG were identified, respectively. These cytosine-phosphate-guanine (CpG) sites included promoter associated cg26263477 annotated to ABCA7 in the STG (p = 1.21 × 10-11), and cg14058329 annotated to the HOXA5/HOXA3/HOXA-AS3 gene cluster (p = 1.62 × 10-9) and cg09448088 (p = 3.95 × 10-9) annotated to MCF2L in the IFG. These genes were previously reported to harbor DMPs and/or differentially methylated regions (DMRs). Previously reported DMPs annotated to RMGA, GNG7, HOXA3, GPR56, SPG7, PCNT, RP11-961A15.1, MCF2L, RHBDF2, ANK1, PCNT, TPRG1, and RASGEF1C were replicated (p < 0.0001). One hundred twenty-one and 173 DMRs associated with pathology in the STG and IFG, respectively, were additionally identified. Of these, DMRs annotated to 30 unique genes were also identified as significant DMRs in the same brain region in a recent meta-analysis, while additional DMRs annotated to 12 genes were reported as DMRs in a different brain region or in a cross-cortex meta-analysis. The significant DMRs were enriched in promoters, CpG islands, and exons in the genome. Gene set enrichment analysis of DMPs and DMRs showed that gene sets involved in neuroinflammation (e.g., microglia differentiation), neurogenesis, and cognition were enriched (false discovery rate (FDR) < 0.05).ConclusionsTwenty-two DMPs and 30 DMRs associated with pathology were replicated, and novel DMPs and DMRs were discovered.

Dataset Information

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

Publications

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

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