BRCA Mutations and the Implications in Transgender Individuals Undergoing Top Surgery: An Operative Dilemma

Previous research involving epithelial ovarian cancer patients showed that, compared to germline BRCA (gBRCA) mutations, somatic BRCA (sBRCA) mutations present a similar positive impact with regard to overall survival (OS) and platinum and PARP (poly (ADP-ribose) polymerase) inhibitor sensitivity. Nevertheless, molecular testing in these studies did not include copy number variation (CNV) analyses of BRCA genes. The aim of this study was to explore the prognostic and predictive role of sBRCA mutations as compared to gBRCA mutations in patients who were also tested for CNVs. Among the 158 patients included in the study, 17.09% of patients carried a pathogenic or likely pathogenic gBRCA variant and 15.19% of patients presented pathogenetic or likely pathogenic sBRCA variants and/or CNVs. Overall, 81.6% of the patients included in this study were diagnosed with a serous histotype, and 77.2% were in advanced stages. Among women diagnosed in advanced stages, gBRCA patients showed better progression-free survival and OS as compared to sBRCA and wild-type patients, whereas sBRCA patients did not show any advantage in outcome as compared to wild-type patients. In this study, the introduction of CNV analyses increased the detection rate of sBRCA mutations, and the resulting classification among gBRCA, sBRCA and wild-type patients was able to properly stratify the prognosis of OC patients. Particularly, sBRCA mutation patients failed to show any outcome advantage as compared to wild-type patients.

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Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

Diagnostics ◽

10.3390/diagnostics11030547 ◽

2021 ◽

Vol 11 (3) ◽

pp. 547

Author(s):

Iolia Akaev ◽

Siavash Rahimi ◽

Olubukola Onifade ◽

Francis John Edward Gardner ◽

David Castells-Rufas ◽

...

Keyword(s):

Ovarian Cancer ◽

Unknown Origin ◽

Parp Inhibitors ◽

Serous Carcinoma ◽

High Grade ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Epithelial Cancers ◽

Pathogenic Variants ◽

Pathogenic Mutations

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

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Should the BCRA1/2-mutations healthy carriers be valid candidates for hematopoietic stem cell donation?

Hereditary Cancer in Clinical Practice ◽

10.1186/s13053-021-00179-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Alberto Fresa ◽

Simona Sica

Keyword(s):

Hematological Malignancies ◽

Conditioning Regimen ◽

Stress Factors ◽

Brca Mutations ◽

Hematopoietic Stem ◽

Mutational Status ◽

Stem Cell Donation ◽

Radiation Treatments ◽

Healthy Carriers

AbstractIt’s still not clear whether the mutational status of BRCA-mutated healthy hematopoietic stem cells (HSCs) donors could have an impact on the engraftment. Comparing the studies present in literature, we focused on the correlation between BRCA mutations and the development of hematological malignancies and Fanconi anemia (FA); then, we explored HSCs types, frequencies, and functions in the presence of BRCA mutations, as well as the reconstitution of hematopoiesis after chemotherapy and radiation treatments. The role of BRCA mutations in the FA showed a possible involvement in the onset of the disease; the mutation carriers, indeed, did not show any sign of the typical phenotype of the FA. BRCA mutational status can be considered as a risk factor for hematological malignancies, but only for secondary malignancies and/or in the presence of bone marrow stress factors. Currently we don’t know if a conditioning regimen could be compensated by BRCA mutated HSCs, even if murine models tried to show the possible differences between fully mutated, haploinsufficient and normal HSCs. Thus, given the downregulating effect of the mutations on hematopoiesis, it could be questionable to use the HSCs of a BRCA-mutated donor in the presence of another available donor with the same compatibility.

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