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Characterization of the D184Y variant in the BRIP1 gene in a family with breast and pancreatic cancer history

Grant number: 19/04927-8
Support type:Regular Research Grants
Duration: July 01, 2019 - June 30, 2021
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Paula Fontes Asprino
Grantee:Paula Fontes Asprino
Home Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil
Assoc. researchers:Anamaria Aranha Camargo ; Cibele Masotti ; Jorge Sabbaga ; Maria Isabel Alves de Souza Waddington Achatz ; Pedro Alexandre Favoretto Galante


About 5-10% of cancers occur in the context of genetic syndromes. People who carry germline genetic variants predisposing to hereditary cancer syndromes are at high risk of developing early-onset tumors within the spectrum of the syndrome. Hereditary breast and ovarian cancer syndrome (HBOC) predisposes to the development of tumors not only in the tissues that name it, but also in other tissues such as the pancreas, prostate, and melanoma. This syndrome is associated with deficiencies in proteins that participate in the homologous recombination system of the DNA repair machinery. With the increased availability of genetic tests, the spectrum of genes related to syndromes such as HBOC is being expanded beyond the notorious BRCA1 and BRCA2. However, the great flood of information describes a large number of variants with unknown clinical significance. In this context, a patient diagnosed with pancreatic cancer, with relevant family history, received the result of a germline cancer-panel test, describing a variant of unknown significance (VUS) in the BRIP1 gene. Here, we intend to verify if the segregation profile of the variant accompanies the phenotype found in the family. We also intend to verify if the mutational profile of the tumors of these individuals present the characteristic mutational signature of tumors with deficiency in the homologous recombination DNA repair system. (AU)