GENETIC PROFILING OF FGFR2 GENE IN EGYPTIAN HEPATOCELLULAR CARCINOMA PATIENTS USING NEXT- GENERATION SEQUENCING
Abstract
Background and objectives: The reliability of fibroblast tyrosine kinase receptor 2 (FGFR2) amplification as the biomarker for FGFR inhibitors in the hepatocellular carcinoma (HCC) is not satisfactory. There is urgent need to comprehensively characterize genetic aberrations of the FGFR2 gene. Simultaneously, we sought to determine the frequency of FGFR2 mutations as a potential tool to detect those alterations association with HCC development and the distribution of the clinical- pathological features of HCC patients with FGFR2 mutations. Patients and methods: Twenty-one patients with newly diagnosed and pathologically confirmed HCC were analyzed using a special Next generation sequencing panel (AmpliSeq). Genetic mutations of FGFR2 gene were identified and analyzed for correlations with clinical-pathological outcome. Results: Recurrent mutations were observed in FGFR2 in 15 (71.4%) patients. When compared to the genomic control, there were twenty-six somatic mutations were detected, of these 22/26 (84.6%) were single nucleotide variants (SNVs), 1/26 (3.8%) was copy number variants (CNVs), 1/26 (3.8%) was multi nucleotide variant substitutions (MVNs) and 2/26 (7.8%) were insertion and deletion (INDELs). Among SNVs, 6/22 (27.3%) were non-synonymous, 4/22 (18.2%) were synonymous, and 12/22 (54.5%) were coding sequence variants. Concerning FGFR2 gene expression data analysis, there is predominance in transcript (52.4%) more than coding transcript (47.6%). The alterations ranged from deleterious to undefinable significance to tolerable deviations. No significant differences were observed between the mutation status of FGFR2 gene, and clinicopathological features of HCC patients. Conclusion: By using bioinformatics, we concluded the roles of FGFR2 genetic variants in the diagnosis and prediction of the HCC development. Taken together, our data underscore to screen HCC patients for FGFR2 aberrations in oncology clinic.
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