title: 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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Semra
authors.initials: S
authors.lastname: Demokan
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chang
authors.forename: Alice
authors.initials: A
authors.lastname: Chuang
authors.forename: Wojciech K
authors.initials: WK
authors.lastname: Mydlarz
authors.forename: Jatinder
authors.initials: J
authors.lastname: Kaur
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.forename: Zubair
authors.initials: Z
authors.lastname: Khan
authors.forename: Tanbir
authors.initials: T
authors.lastname: Khan
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Ostrow
authors.forename: Mariana
authors.initials: M
authors.lastname: Brait
authors.forename: Mohammad O
authors.initials: MO
authors.lastname: Hoque
authors.forename: Nanette J
authors.initials: NJ
authors.lastname: Liegeois
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Wayne
authors.initials: W
authors.lastname: Koch
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D044023:Receptor, Endothelin B / Q000235:genetics*; D012463:Saliva; D012469:Salivary Glands / Q000473:pathology; D055815:Young Adult
chemical_list: C094065:KIF1A protein, human; D044023:Receptor, Endothelin B; D016547:Kinesins