The link between FGFR۱/FGFR۳ and Ras gene mutations and the pathological tumor grades in oral squamous cell carcinoma in Iranian patients

Introduction Fibroblast growth factors (FGFRs) play a major role in development of malignancy in different tissues. In the present study, we aimed to determinate mutations in specific exons in FGFR۱, FGFR۳ as well as in the hot spot of the H-ras gene in tissue biopsies of oral cavity squamous cell carcinoma (OSCC). In addition, the expression of the protein products of these genes was also determined in the tumor biopsies. The gene mutations of the H-ras, FGFR۱ and FGFR۳ patients’ was evaluated in terms of demographic information and pathological grade of tumors. Methods: In this study, ۶۶ surgically removed tumor biopsies from OSCC patients and ۳۲ normal biopsies (gingival tissue) were analyzed. DNA was extracted from the biopsies and gene mutations in selected exons of H-ras, FGFR۱ and FGFR۳ were determined using Sanger’s sequencing. Histological and immunohistological (IHC) examinations were carried out on tissue samples. Results: The frequency of H-ras mutation in exon ۲ was ۵۳.۲%. The mutation rate in exon ۱۳ of FGFR۱ and exon ۷ FGFR۳ was ۳۲.۲% and ۲۷.۴%, respectively. The rate of mutations in selected exons in H-ras and FGFRs (۱,۳) in high-grade (Poorly Differentiated) tumors was ۱۰۰% and ۷۷% respectively. The frequency of mutations in three genes H-ras, FGFR۱, FGFR۳ in patients with smoking history were ۷۴.۲%, ۴۲.۸% and ۳۷.۱%, respectively, which was statistically significant compared to non-smokers (P< ۰.۰۵). IHC data show that accumulation of H-ras, and FGFRs proteins were significantly higher in tumor biopsies of OSCC compared to that measured in normal tissues. Conclusion: This study showed that frequency of gene mutations in specific exons of H-ras and two types of FGFR genes in tumor samples in Iranian patients are associated with tumor grade as well as over-expression of the protein products. Association of the Ras and FGFRs mutations and activation with the grade of OSCC tumors provide useful information on the mechanisms underlying progression of OSCC tumors.

کلیدواژه ها:

Oral squamous cell carcinoma ، biomarker ، H-ras ، FGFRs