Exome sequencing revealed comparable frequencies of RNF43 and BRAF mutations in Middle Eastern colorectal cancer.

Mutation-induced activation of Wnt-ß Catenin signaling pathway is frequent in CRC. The E3 ubiquitin ligase, RNF43, has been reported to negatively regulate the Wnt signaling pathway and RNF43 mutations are frequently seen in CRC. However, its role in Middle Eastern CRC remains unclear. Therefore, we employed Exome and Sanger sequencing technology to assess the frequency of RNF43 mutations and its association with other clinico-pathological features in Middle Eastern CRC. RNF43 mutations were found in 5.9% (13/220) of CRC cases and was inversely correlated to APC and TP53 mutations. A strong association of RNF43 mutations with right sided and sporadic microsatellite instable (MSI) CRC was observed. No association was identified between RNF43 mutation and other clinico-pathological features including BRAF mutation, age, tumor histological subtype, tumor grade or patients' prognosis. Multivariate logistic regression analysis revealed that MSI status and wild type APC were independent predictor of RNF43 mutation. We conclude that RNF43 mutations occur in Middle Eastern CRC at comparable frequencies with BRAF mutations and represent a distinct molecular subtype which further enhances our understanding of how different mutational subsets of Wnt tumor suppressor genes link to distinct tumor characteristics, which might be considered for treatment strategies for CRC patients.

Prevalence of fragile histidine triad expression in tumors from saudi arabia: a tissue microarray analysis.

AIM: The fragile histidine triad (FHIT) gene was discovered and proposed as a tumor suppressor gene for most human cancers. It encodes the most active common human chromosomal fragile region, FRA3B. We studied the prevalence of loss of FHIT expression in various tumors and correlated its loss with various clinicopathologic features. METHODS: To determine whether the absence of FHIT expression correlates with clinical variables such as grade, stage, and survival time, we assessed FHIT expression using immunohistochemistry. More than 1,800 tumors from more than 75 tumor categories were analyzed by immunohistochemistry in a tissue microarray format. RESULTS: Loss of FHIT expression ranged from 19% in ovarian tumors to 67% in lung cancers. Clinical and pathologic features like grade, stage, tumor size, and lymph node metastasis showed correlation with loss of FHIT expression in some tumors. No difference was seen in the survival patterns and loss of FHIT expression in any of the tumor groups studied. CONCLUSIONS: Loss of FHIT expression is an ubiquitous event in the multistep, multifactorial carcinogenesis process. FHIT may be altered at different stages in different types of cancers. Most of the tumors with a wider prevalence of loss of FHIT expression as an early event show a correlation with clinicopathologic features. However, in some of the tumors, FHIT expression is lost as a late event and is only seen in a fraction of the tumors.