P-21: Low Mutation Rate in Exon 15 of the APC Gene in Patients Affecting Sporadic Colorectal Cancer in the Khuzestan Province


Hasanpour M *, Galehdari H , Masjedi Zadeh A ,

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Objective: Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. The incidence of colorectal cancer in Iran is 7.5 in 100000; however several studies have shown a remarkable increase in the incidence rate of CRC during recent years in Iran. The majority of CRC cases are sporadic that occur in persons without a family history of CRC and are caused by somatic mutations in colon and rectum. Adenomatous polyposis coli (APC) tumor suppressor gene encodes a multifunctional protein that acts as a gatekeeper in the Wnt signal transduction pathway. Mutations in the APC gene have reported in up to 80 percent of sporadic CRC cases. The APC gene consists of 15 exons, the largest of which is exon 15, which includes more than 75% of the coding sequence of the gene. Exon 15 is the most common target for both somatic and germline mutations. Mutations in the APC gene initiate the process of colorectal tumorigenesis. This study evaluates the presence of mutations in exon 15 of the APC gene in sporadic CRC patients. Materials and Methods: Tumor and adjacent normal tissue samples were obtained from 26 patients referred to the Mehr and the Emam Hospitals in Ahvaz. The DNA from fresh frozen tissue was extracted using proteinase K digestion and salting out method. We designed four primer pairs due to amplifying four overlapping fragments (codons 654-885, 853-1242, 1213-1482 and 1404-1613) of exon 15. Direct sequencing was used for analyzing of four amplified fragments. Results: We found three frameshift mutations c.2804dupA, c.4317delT and c.4464_4471del, two missense mutations T1079S and E1317Q and two nonsense mutations Q1367X and R1450X in six patients. One of patients showed two mutations. We additionally detected the T1493T polymorphism in 19 patients. Conclusion: In this study, mutations were detected in 6 (23%) of 26 CRC patients. But the mutation frequency is lower in comparison to the previous studies from other countries. According to the previous reports, the identified five frameshift and nonsense mutations are pathogenic and lead to truncated APC protein. The pathogenicity of the T1079S missense mutation is unknown but the E1317Q mutation is considered being a predisposing variant for the CRC progression