title: Loss of protein expression and recurrent DNA hypermethylation of the GNG7 gene in squamous cell carcinoma of the head and neck.
abstract: Although down-regulation of GNG7 in cancer was reported before, its role in carcinogenesis is poorly understood. It belongs to a family of large G-proteins that may be involved in cell-contact-induced growth arrest and function in tumor suppression. In the present study, we stained immunohistochemically 188 tumors derived from larynx or floor of the mouth for GNG7 protein and confronted it with clinicopathologic data. Moreover, we performed bisulfite pyrosequencing to analyze GNG7 promoter methylation. We identified recurrent loss of GNG7 protein expression in 68/188 (36%) cases and promoter hypermethylation in (42/98; 43%) primary tumors, predominantly in young patients (p < 0.001). Loss of GNG7 expression correlated with hypermethylation of GNG7 promoter region (p < 0.001). Moreover, loss of GNG7 protein expression correlated with tumor size (p = 0.012) and lack of cervical metastasis (p = 0.02) whereas sustained expression correlated with keratinization (p = 0.008). Taken together, loss of GNG7 protein expression is a frequent event in head and neck cancer. Moreover, our data suggest that hypermethylation of the promoter region of GNG7 is probably the mechanism of the observed inactivation.
authors.affiliation: Institute of Pathology, University Hospital, 60590 Frankfurt, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hartmann
authors.forename: Marcin
authors.initials: M
authors.lastname: Szaumkessel
authors.forename: Itziar
authors.initials: I
authors.lastname: Salaverria
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kiwerska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Gawecki
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bodnar
authors.forename: Andrzej
authors.initials: A
authors.lastname: Marszalek
authors.forename: Julia
authors.initials: J
authors.lastname: Richter
authors.forename: Damian
authors.initials: D
authors.lastname: Brauze
authors.forename: Natalia
authors.initials: N
authors.lastname: Zemke
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jarmuz
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szyfter
authors.forename: Maciej
authors.initials: M
authors.lastname: Giefing
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary
chemical_list: D004273:DNA, Neoplasm; C527544:GNG7 protein, human; D044388:GTP-Binding Protein gamma Subunits; D007633:Keratins