Two novel variants in the 3′UTR of the gene in familial breast and/or ovarian cancer

International audienceFor the majority of breast and/or ovarian cancer patients tested for / genes, mutation screening of the coding regions remains negative. MicroRNAs which negatively regulate mRNA translation by binding to 3′ untranslated region (3′UTR) are implicated in cancer. Genetic changes in the 3′UTR of several genes were reported to be associated with higher susceptibility to particular tumor types. The aim of this study was to analyze the 3′UTR in patients tested negative for / deleterious mutations, in order to find variants implicated in the decrease of expression through modification of miRNA binding. Genotyping analyses were performed on genomic DNA of 70 negatives index cases, selected among patients with breast or ovarian cancer, less than 50 years old, with a strong family history. The co-occurrence of the identified variants with deleterious mutations was then determined in a control population of 210 patients. A luciferase gene reporter assay was used to investigate the impact of the variants on the gene expression. Two novel variants, c.*750A>G and c.*1286C>A, were identified in the 3′UTR of gene, in two patients. The former was found three times in the control population, whereas the latter was absent. The used functional assay did not reveal any effect on the luciferase expression. This study reveals a weak genomic variability in the 3′UTR of the gene. All together, the results led us to classify the variant c.*750A>G as probably neutral, the variant c.*1286C>A remaining unclassified