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Hereditary breast and ovarian cancer syndrome (HBOC) is partly due to the presence of mutations in the  BRCA  genes. Triple-negative (TN) breast cancer (BC) shares histological characteristics with germline  BRCA1  mutation-associated tumours. We have investigated the metabolic profiles of human breast cancer (BC) cell lines carrying  BRCA1  pathogenic mutations by non-targeted liquid chromatography coupled to mass spectrometry technology. Based on our  in vitro  results, we performed a targeted metabolomic analysis of plasma samples from TN HBOC patients taking into account their  BRCA1  genotype.  BRCA1  promoter hypermethylation and the BRCAness phenotype of BC cell lines were also studied. The purpose of this study was to determine the metabolic signature of HBOC syndrome and TNBC patients and to evaluate the potential contribution of the metabolites identified to the genetic diagnosis of breast cancer. The present results show the existence of a differential metabolic signature for BC cells based on the BRCA1 functionality. None of the studied BC cell lines presented hypermethylation of the  BRCA1  promoter region. We provide evidence of the existence of free methylated nucleotides capable of distinguishing plasma samples from HBOC patients as  BRCA1 -mutated and  BRCA1  non-mutated, suggesting that they might be considered as BRCA1-like biomarkers for TNBC and HBOC syndrome.

Metabolomics reveals novel blood plasma biomarkers associated to the BRCA1-mutated phenotype of human breast cancer