Detection of P۵۳ Gene Exons ۵ and ۶ Mutations Among East Azerbaijani Women with Breast Cancer

Background and Objectives: Breast cancer (BC) is the most common invasive malignancy affecting women worldwide. The tumor-suppressor P۵۳ gene (P۵۳) is frequently mutated in breast tumors. To use P۵۳ as a target for therapy, it is important to accurately assess p۵۳ mutation status in tumor samples. Materials and Methods: A total of ۱۰۲ tumor samples were collected from breast cancer patients referred to Tabriz hospitals between the ۲۰۰۷-۲۰۰۹ period. DNA was extracted by Proteinase K– Isopropanol method and then performed amplification and sequencing of P۵۳ from exons ۵ and ۶. Results: Mutations in the P۵۳ gene were detected in ۱۷.۶% of the patients. Including ۷ polymorphisms (۶.۶۸%) and ۱۱ mutations (۱۰.۷۸%). Overall, ۱۸.۲% of the mutations were found in codons ۱۶۰ (ATG>AAG) and ۱۶۳ (ATC>AAG) in exon ۵. Also ۸۱.۸% of the mutations observed in exon ۶: codon ۱۹۳(CAT>AAT), codon۱۹۵ (ATC>TTC), codon ۱۹۵ (ATC>AAC), codon ۱۹۸(GAA>TAA), codon ۲۲۰ (TAT>TGT), codon ۲۱۳ (CGA>CTA), and codon ۲۱۴ (CAT>CG). No alteration observed in intron۵ and all of polymorphism detected in ۱۳۳۹۹A>G nucleotide of exon ۶. The majority of detected mutations are missense that located on DNA-binding domain of P۵۳. This type of mutation usually leads to the production of a mutant protein with a compromised structure and altered DNA-binding capacity. Conclusion: This is the first report of its kind from the East Azarbaijan region. Our results indicate a rather high frequency of exon ۶ mutations in P۵۳ among patients with breast cancer. Furthermore, the mutation pattern appears differs from other regions. However, further studies are needed to determine the role of P۵۳ mutations in breast cancer development.

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Keywords: Breast cancer , P۵۳ gene , East Azarbaijan