BAP1-deficient meningioma presenting with trabecular architecture and cytokeratin expression: a report of two cases and review of the literature

AimsBRCA (BReast CAncer gene)-associated protein 1 (BAP1), encoded by the BAP1 gene, a tumour suppressor that is lost in several cancers. Importantly, such mutations have been shown to be susceptible to poly (ADP-ribose) polymerase (PARP) inhibition in preclinical studies, offering hope for targeted therapy. While rare, BAP1 loss has been observed in a subset of rhabdoid and papillary meningioma and is associated with earlier recurrence. We seek to add to the literature on this rare disease and advocate for more routine BAP1 testing.MethodsWe present a report of two cases of BAP1-deficient meningioma and review the available literature on this rare entity.ResultsBoth cases present with a distinct trabecular architecture without rhabdoid or papillary features. Interestingly, both also presented with radiographic and histopathological findings unusual for meningioma. While immunohistochemistry and genetic sequencing confirmed BAP1 loss, DNA methylation analysis was required to confirm the final diagnosis.ConclusionsWe suggest that BAP1-deficient meningioma should be considered in the differential diagnosis of extra-axial central nervous system (CNS) tumours with atypical imaging or histopathological features and that BAP1 loss may constitute a clinically important meningioma subtype with opportunities for targeted therapy.

Targeting BRCA and DNA Damage Repair Genes in GI Cancers: Pathophysiology and Clinical Perspectives

Mutated germline alleles in the DNA damage repair (DDR) genes “breast cancer gene 1” (BRCA1) and BRCA2 have originally been identified as major susceptibility genes in breast and ovarian cancers. With the establishment and approval of more cost-effective gene sequencing methods, germline and somatic BRCA mutations have been detected in several cancers. Since the approval of poly (ADP)-ribose polymerase inhibitors (PARPi) for BRCA-mutated cancers, BRCA mutations gained rising therapeutic implications. The impact and significance of BRCA mutations have been evaluated extensively in the last decades. Moreover, other genes involved in the DDR pathway, such as ATM, ATR, or CHK1, have emerged as potential new treatment targets, as inhibitors of these proteins are currently under clinical investigation. This review gives a concise overview on the emerging clinical implications of mutations in the DDR genes in gastrointestinal cancers with a focus on BRCA mutations.

Using Breast Cancer Gene Expression Signatures in Clinical Practice: Unsolved Issues, Ongoing Trials and Future Perspectives

The development of gene expression signatures since the early 2000′s has offered standardized assays to evaluate the prognosis of early breast cancer. Five signatures are currently commercially available and recommended by several international guidelines to individualize adjuvant chemotherapy decisions in hormone receptors-positive/HER2-negative early breast cancer. However, many questions remain unanswered about their predictive ability, reproducibility and external validity in specific populations. They also represent a new hope to tailor (neo)adjuvant systemic treatment, adjuvant radiation therapy, hormone therapy duration and to identify a subset of patients who might benefit from CDK4/6 inhibitor adjuvant treatment. This review will highlight these particular issues, address the remaining questions and discuss the ongoing and future trials.

Significant Diagnostic and Prognostic Value of FLAD1 and Related MicroRNAs in Breast Cancer after a Pan-Cancer Analysis

The identification of biomarkers plays an important role in the diagnosis and prognosis of cancers. In this study, we explored the diagnostic and prognostic value of the FLAD1 expression across pan-cancer analysis from online databases (Oncomine, cBioPortal, Breast Cancer Gene-Expression Miner, UALCAN, GEO, BCIP, TNMplot, ENCORI, Kaplan-Meier Plotter, and LinkedOmics). We found that FLAD1 was overexpressed in a number of different kinds of cancers, especially in breast cancer, and higher FLAD1 expression level was associated with the HER+, p53 mutant, node-involved, NPI stage 3, basal-like, and triple-negative groups compared with the other subgroups of breast cancer. The FLAD1 expression levels were higher in patients that were 21–40 years old than those in patients of other ages and were higher in the African-American group than in the Caucasian group. We also analyzed the FLAD1-related microRNAs and their prognostic values in breast cancer. This study highlights the significance of FLAD1 in cancers and provides evidence for its potential as a biomarker for the diagnosis and prognosis of cancers.

Oncoplastic Surgery in the Large-Breasted Breast Cancer gene Patient: A Staged Step to Enable Nipple Sparing Mastectomy

Patients with macromastia and/or moderate-severe ptosis who desire mastectomy are typically offered skin sparing mastectomies. Recent technical advances have broadened the inclusion criteria to allow for nipple sparing mastectomy (NSM) in this population; however, they have been limited to patients with unifocal disease. We report on the multidisciplinary approach used to offer a NSM to a patient with multicentric triple-negative breast cancer and symptomatic macromastia with severe ptosis in the setting of positive genetic testing. We discuss the combination of a staged oncoplastic approach with neoadjuvant and adjuvant chemotherapy, as well as the foundations of these approaches. We encourage further research and inclusion of patients such as ours in the criteria for NSM.

Breast cancer

Breast cancer (BC) is a malignant tumor originating from the epithelium of the breast tissue. There is no single etiological factor in the development of breast cancer. In 310% of patients with breast cancer, the development of the disease is associated with the presence of mutations in the breast cancer gene (BRCA) 1, BRCA2, CHEK, NBS1, TP53. In other patients, breast cancer is sporadic.