BRCA1 hypermethylation

These data suggest that a gene panel (BRCA1/MGMT/GSTP1) can be used to support the diagnosis and screening of Vietnamese patients' BC with a sensitivity of 70%, and a specificity of 85%.

Finally, we observed a concordance (60%) in BRCA1 promoter hypermethylation status between malignant breast tumors and their paired histologically normal adjacent tissues. This study highlights the role of BRCA1 promoter hypermethylation as a potential useful biomarker of aggressiveness in MBTs and as an early marker of genomic instability in both histological NATs and BBLs.

109 had chemotherapy (>90% with sequential epirubicin + cyclophosphamide and a taxane, EC–T) according to national guidelines either as NAC (32%) or adjuvant (68%) therapy. Conclusions BRCA1met is associated with young age in TNBC but hold no predictive nor prognostic value in this patient cohort. We observe a difference in BRCA1met patterns and BRCA1 mRNA expression in NAC patients with RD that may potentially be related to treatment resistance.

We performed the functional and dynamic RAD51 test on 164 patients with high-grade serious OvC, enrolled in the MITO16A/MANGO OV2 trial and treated with first-line therapy containing carboplatin, paclitaxel, and bevacizumab. Our preliminary results confirmed the feasibility of the RAD51 functional assay on primary untreated OvC. The association between HRD by RAD51 and TIL content encouraged to investigate the efficacy, in clinical trials, of the combination of PARPi and immune-checkpoint inhibitors on selected patients (i.e. HRD by RAD51 and TIL high).

OC patients with high levels of BRCA1 hypermethylation are very likely to have high GIS and therefore represent good candidates for PARPi treatment. These results may be relevant to other tumor types for HRD prediction.

109 had chemotherapy (>90% with sequential epirubicin + cyclophosphamide and a taxane, EC–T) according to national guidelines either as neoadjuvant (32%, NAC) or adjuvant (68%, ACT) therapy. Conclusions BRCA1met is associated with young age in TNBC but hold no predictive nor prognostic value in this patient cohort. We observe a difference in BRCA1met patterns in NAC patients with RD that may potentially be related to treatment resistance.

Treatment with demethylating agents, decitabine and GSK-3484862, resulted in a heterogenous methylation pattern of me BRCA1 , which was associated with BRCA1 re- expression...This study is designed to reveal novel targetable pathways capable of overcoming PARPi resistance in me BRCA1 cancers. Improved understanding of mechanisms impacting epigenetic silencing and methylation stability of BRCA1 may inform future combination therapies and guide trials of epigenetic modulating therapies in HGSOC.

Further studies are ongoing in our laboratory to investigate whether BRCA1 hypermethylation in blood correlates with BRCA1 hypermethylation in the corresponding tumour samples.

We conclude that BRCA1 gene is significantly hypermethylated in EOC patients and thus can prove to be a noninvasive diagnostic tool. Our results provide prefatory evidence that epithelial ovarian epigenome can be influenced by dietary nutrients.

Regarding group B, patients with disease control exhibited mutations in FANCL, FANCA and the RAD51D genes or RAD51C methylation; mutations in HRR genes and epimutations in RAD51C were associated with disease control through platinum-based chemotherapy. As such, apart from well-characterized alterations in BRCA1/2, a more comprehensive evaluation of HRD should be considered in order to enlarge the selection of patients with mTNBC that could benefit from platinum-based chemotherapy.

In a large cohort of 178 patients, none had tumors harboring the previously identified c.-107A > T SNV in BRCA1. We therefore can conclude that the germline SNV is not pervasive in patients with tumor BRCA1 promoter hypermethylation.

We comprehensively analyzed HRD scores and their association with mutations in HRR genes in common cancer types. Our study identifies important parameters influencing HRD measurement and argues for an integration of HRDsum score with specific mutational profiles.