BAP1 deletion

By elucidating the interaction between BAP1 and LDHA and the subsequent effects on lactate production in melanoma cells, this work provides insights into the mechanism of BAP1-mediated metabolic regulation. Furthermore, it may provide novel directions for the clinical treatment of BAP1-mutant melanoma.

Our study elucidates an unrevealed mechanism by which BAP1 regulates immune therapy response in PDAC via HSF1 inhibition, and providing promising therapeutic strategies to address immune insensitivity in BAP1-deficient PDAC.

BAP31 up-regulated the expressions of ICAM1 and VCAM1 in endothelial cells leading to sepsis-associated organ injury. This may be involved in activation of TLR signaling pathway, TAK1 pathway, and PI3K-AKT signaling pathway.

Hi-C revealed chromatin topology changes associated with the upregulation of PRAME, an independent prognostic biomarker in UM, and a potential therapeutic target. Our findings illustrate how multi-omics approaches can improve our understanding of tumorigenesis and reveal two distinct mechanisms of gene expression dysregulation in UM.

Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.

Notably, out of 196 mesenchymal neoplasms of gynecologic origin, BAP1 homozygous deletion was only found in adenosarcomas (P = 0.0003). This study demonstrates that high-grade adenosarcomas are heterogeneous at the molecular level and are characterized by genomic instability and TP53 mutations; ATRX loss may be involved in high-grade transformation of low-grade adenosarcoma; and BAP1 inactivation appears to be a specific pathogenic driver in a subset of adenosarcomas.

As her triple negative tumor was shown to be PD-L1 positive, the patient was treated with combination of atezolizumab and nab-paclitaxel. This case strengthens the evidence for including breast cancer in the BAP1 cancer syndrome tumor spectrum with implications for future cancer prevention programs. It also indicates immune checkpoint inhibitors might prove to be an effective treatment for BAP1-deficient breast cancer.

The co-occurrence of these two mutations reduces invasion of UM cells in zebrafish xenograft models and suppresses growth of melanoma xenografts in nude mice. Our findings provide a mechanistic explanation for the mutual exclusivity of BAP1 and SF3B1 mutations in human UM.

BAP1 deletion in the primary tumor is associated with uveal melanoma metastasis, but it cannot always be resolved by bulk DNA sequencing of heterogeneous tumors. Here, we show that assessment of BAP1 methylation is an accurate and readily clinically actionable assay to accurately identify high-risk uveal melanoma patients.

To conclude, we have reported histopathological features of two cutaneous melanocytic tumours with loss of BAP1 expression to- gether with a germline BAP1 mutation in a case of BAP1-associated cancer susceptibility syndrome. If a Wiesner nevus is revealed and the patient has both multiple cutaneous tumours, with or without relevant family history, genetic tests for tumour predisposition syndrome are recommended.

Alterations in BAP1 in MPM were a negative predictor for response to chemotherapy and could possibly be used as a companion biomarker for treatment decision.

Through a survey of biomarkers in 124 cases MPM at Pham Ngoc Thach Hospital from 2015-2019 we have brought the following statements: For diagnosis: There is evidence of presence of asbestos body and SV-40 and the IHC markers of Calretinin, Glut-1 and WT-1 have been the highest expressions in the cases of MPM and have been the best values in epidemiological diagnosis and positive diagnosis of MPM. For treatment: The most important gene expressions have been p16 Deletion and BAP1 and a positive PD-L1 ratio with two markers: 22C3 and SP263. This also leads to the possibility of targeted application and immunotherapy for MPM.