Computational Analysis of BRCA1 Mutations in Pediatric Patients with Malignancies and Their Mothers

• Main Authors: Lambrou, George I., Barbounaki, Ioanna, Tzortzatou-Stathopoulou, Fotini, Petropoulou, Ourania, Katrakazas, Panagiotis, Iliopoulou, Dimitra, Koutsouris, Dimitrios-Dionysios
• Format: Conference Proceeding
• Language: English
• Subjects: BRCA1; BRCA2; Cancer; Childhood Acute Lymphoblastic Leukemia; Computational Analysis; Gene expression; Mutations; Neoplasms; Pediatrics; Proteins; Sociology; Statistics
• ISSN: 2372-9198
• DOI: 10.1109/CBMS.2017.111

Breast and ovarian cancers are the most prevalent type of malignancies amongst women. Similar incidence appear in childhood malignancies, where the basic ontogenetic mechanisms still remain to be elucidated. Such approaches, of relating mothers cancer mutations with the prevalence of childhood cancer in their offspring could prove useful in the prognosis, early detection and therapy of childhood malignancies. The aim of the present study was to use computational and bioinformatics tools to investigate the incidence of mutations in mothers with children suffering from neoplasms. Genes were examined for mutations and in particular, those were BRCA1, RAS family genes, TP53 and FLT3. Mutations were initially detected using PCR and multiplex Polymerase Chain Reaction (PCR) methodologies. Gene expression was detected using quantitative Reverse Transcription PCR (qRT-PCR) methodologies and results have been confirmed with the sequencing method. Following experimental analysis, bioinformatics analyses have been performed. In the case of positive identification of mutations, molecular modelling was used in order to study the effects of the mutations on the BRCA protein and subsequent effects on binding to BARD1, a signaling molecule down-stream of BRCA1, which participates in DNA repair pathways. Concluding, it appeared that the presence of a mutation in the aforementioned genes is not adequate for the disease to progress, yet it can be considered as a serious factor for disease progression. Thus, it appears that this phenomenon is of extreme interest and it should be further investigated in a larger patient cohort.