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.

hTERT promoter methylation status in peripheral blood leukocytes as a molecular marker of head and neck cancer progression

“…In case of several head and neck cancer-related genes (such as SST, CXXC4, DACT2, RASSF1A, MGMT1, SFRP1, GNG7), altered methylation patterns were identified (Hartmann et al 2012;Misawa et al 2015;Koutsimpelas et al 2012;Paluszczak et al 2017;Alsofyani et al 2017). However, most significant disadvantage of those studies was employment of tissue specimens as primary material, which limits diagnostic value of these findings due to high invasiveness during sample collection and laborious microdissection procedures allowing to select cancer cells from the stroma of the tumor.…”

Epigenetic alterations in metastatic cutaneous carcinoma

“…In these samples, MYCL2 was unmethylated in metastatic BCCA and methylated in non-metastatic BCCA, suggesting that methylation at these loci could be used as biomarkers of metastatic potential. Of interest in the gene list with borderline significance, GNG7 , involved in transmembrane signaling, has been shown to be hypermethylated in head and neck squamous cell carcinoma (40) and fibroblast growth factor 9 ( FGF9 ) is upregulated in cutaneous squamous cell carcinomas (41). …”

“…In these samples, MYCL2 was unmethylated in metastatic BCCA and methylated in nonmetastatic BCCA, suggesting that methylation at these loci could be used as biomarkers of metastatic potential. Of interest in the gene list with borderline significance, GNG7, involved in transmembrane signaling, has been shown to be hypermethylated in head and neck SCC 39 and fibroblast growth factor 9 (FGF9) is upregulated in cutaneous SCCs. 40 IHC staining for a range of proteins, including EGFR and RUNX3, did not reveal significant differences in expression when comparing primary tumors that metastasized and those that did not.…”

Identification of a four-gene panel predicting overall survival for lung adenocarcinoma

“…GNG7 (G protein subunit gamma 7), a novel possible tumor suppressor gene, is proved to be down-regulated in various carcinoma, including head and neck squamous cell carcinoma, clear cell carcinoma of kidney, pancreatic cancer, oesophageal cancer, lung adenocarcinoma et al [38][39][40][41][42].…”