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

• Published in: Scientific reports 2022-07, Vol.12 (1), p.13098-13098, Article 13098
• Main Authors: Siraj, Abdul Khalid, Bu, Rong, Masoodi, Tariq, Parvathareddy, Sandeep Kumar, Iqbal, Kaleem, Al-Haqawi, Wael, Al-Dossari, Hassan, Azam, Saud, Qadri, Zeeshan, Annaiyappanaidu, Padmanaban, Al-Dayel, Fouad, Al-Kuraya, Khawla Sami
• Format: Article
• Language: English
• Subjects: 631/67/1504/1885; 631/67/68; Adenomatous polyposis coli; Colorectal cancer; Colorectal carcinoma; Humanities and Social Sciences; Kinases; Microsatellite instability; multidisciplinary; Mutation; p53 Protein; Patients; Regression analysis; Science; Science (multidisciplinary); Signal transduction; Tumor suppressor genes; Tumors; Ubiquitin; Ubiquitin-protein ligase; Wnt protein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-17449-9

Mutation-induced activation of Wnt -β 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.