Genética hereditária: pesquisas atuais

Abstrato

Two Novel Somatic Mutations in Exon 15 of the Adenomatous Polyposis Coli Gene in Iranian Familial Adenomatousis Polyposis Coli Patients

Vazifehmand R

Background: The Adenomatous Polyposis Coli (APC) gene is considered as a gatekeeper in colorectal tumorigenesis. 60% of somatic mutations in the APC gene are concentrated in a region called the Mutation Cluster Region (MCR). In this study, our objective was to perform the genetic analysis of two patients (index patients) who had been selected by colorectal cancer features, and to identify the genetic changes in the MCR region of the APC gene. Following discussions about the disease, the patients (index persons) agreed to a further genetic evaluation.
Materials and methods: Mutation analysis of the MCR, which spans codons 1286-1513, was performed on the paraffin-embedded cancerous tissue samples using macro dissection, nested PCR and direct sequencing of purified PCR fragments.
Results: In our study, two new somatic mutations detected in these patients. In one patient, we have detected a CGA to TGA as a Nonsense mutation that lead to Arg to premature Stop codon at the 4507 nucleotide position (Codon 1503) and in another patient, we describe a G→A Transition (ACG to ACA) at nucleotide position 4638 in exon 15 (MCR) which causes a silent mutation since both normal and mutated alleles encode a Thr residue at codon 1546. These mutations have not been described previously.
Conclusion: This observation could suggest differences in the frequency of pathological mutations in APC among different populations; however, epidemiological studies must be performed to confirm this theory which it is not the aim of our present work.