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The secreted frizzled-related proteins (SFRPs) genes are unmethylated in normal colorectal mucosa tissue but aberrant methylation profiles can be detected in colorectal cancer (CRC), adenomas, and in aberrant crypt foci. The aim of the current study was to clarify whether SFRP2 methylation and K-ras structural mutation in fecal DNA can be found in stool and tumoral tissues of individuals with fistula-associated mucinous type anal adenocarcinomas (MTAA).Two man patients (68 and 56 years old) were treated for anorectal fistula in the surgical department. Patients were evaluated for clinical findings, tumoural tissue samples were examined histopathologically and DNA from fecal and tumoral tissue samples were isolated. K-ras mutation and promoter hypermethylation of SFRP2 gene in tumoral tissues were assessed by methylation-specific PCR based stripAssay hybridisation technique (Me-PCR) and compared to the healthy controls. Fecal and tumoural tissue samples from both patients were found to be fully hypermethylated profiles for SFRP2 gene and combined point mutations were detected in codon 12 and 13 of K-ras proto-oncogene. The current results showed that the combined effects of somatic mutations in K-ras and epigenetic alterations in SFRP2 genes may play an active role in the development of mucinous type anal adenocarcinoma.

internal medicine

Epigenetic Inactivation of Tumor Suppressor SFRP2 and Point Mutation in KRAS Proto-Oncogene in Fistula - Associated Mucinous Type Anal Adenocarcinoma: Report of Two Cases