الملخص الإنجليزي
Gastric cancer (GC) is the second leading cause of cancer-related deaths and the fourth most common cancer worldwide. Gastric adenocarcinoma is a very heterogeneous disease with multiple environmental etiologies and alternative pathways of carcinogenesis. Genetic alteration such as mutations in tumor suppressor genes contributes to the pathogenesis of GC. It has been shown recently that FAT4, a member of FAT cadherin family, exerts tumor suppressor activity. Mutations in the cell adhesion gene, FAT4, were reported in several human cancers including melanoma, pancreatic, head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma associated with Hepatitis C virus (HCV), and gastric adenocarcinoma. The aims of this study are to identify the incidence rate of somatic mutation of FAT4 gene in a cohort of Omani patients diagnosed with gastric adenocarcinoma and to correlate the detected FAT4 mutations with clinicopathological features and survival.
DNA was extracted from 75 tumor blocks of patients affected with GC. The hot spots of FAT4 gene were amplified using polymerase chain reaction (PCR) and analyzed by sequencing. We have detected missense mutation in 8% of gastric cancers (6/75) and FAT4 genomic deletions in exon17 in 41% of gastric tumors (31/75). Up to our knowledge, the six nonsynonymous mutations are novels. They are located in the cytoplasmic domain of FAT4 cadherin and the tertiary structures changed in two mutant domains H4845R and G4900R. However there was no association between FAT4 alterations and clinicopathological features and no prognostic value in terms of overall survival in univariate and multivariate analysis. The current study suggests that FAT4 gene alterations in particular mutations (some of which are novel) are detected in Omani patients with gastric adenocarcinoma and may have a role in carcinogenesis but no significant prognostic value.
