RKIP and BRAF aberrations in human nasal polyps and the adjacent turbinate mucosae
Bizakis, John G.
Spandidos, Demetrios A.
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Background: Little is known about the implication of BRAF and RKIP expression, or about the incidence of BRAF mutations in the formation of nasal polyposis. Objectives: To determine the expression levels of the genes BRAF and RKIP, and to inspect the frequency of BRAF mutations in exons 11, 14 and 15 in human nasal polyps (NP). Patients and methods: We analyzed 24 human NP specimens and their adjacent inferior and middle turbinates (AIT and AMT), as well as 14 control subjects [bearing 14 Control Inferior Turbinates (CIT) and 14 Control Middle Turbinates (CMT), in total]. The expression pattern of BRAF and RKIP was assessed with real-time RT-PCR. A real-time allele-specific PCR method, in combination with direct sequencing, was performed in order to inspect the frequency of the V600E mutation in exon 15, and to examine mutation status within exons 11 and 14. Results: The control mucosae presented significantly higher mRNA levels for both genes, compared to the NP and the AIT-AMT. Moreover, in NP, AIT and AMT, RKIP was found to present higher mRNA levels, in relation to the equivalent values of the BRAF gene (P = 0.003 in NP; P < 0.001 both in AIT and AMT). No mutation was detected in exon 14, whereas a silent mutation (A1380G, G460G) was noted for one NP sample in exon 11. Another NP sample was found to carry two mutations, one T1799A (V600E) and one A1801G (K601E). A significant co-expression of the two genes was noted in NP (P = 0.012) and AIT (P = 0.019). Conclusion: The results of the expression levels of RKIP and BRAF, reflect the strong connection between the two genes. RKIP could play an important role in the down-regulation of wild-type BRAF, serving thus as an endogenous inhibitor of the MAPK pathway in nasal polyps and their adjacent turbinate mucosa.