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BAP1 inhibits Mesothelioma. 22 / 22
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"Inactivation of BAP1 sensitises tumour cells to EZH2 inhibition, which has been shown to substantially inhibit tumour growth in BAP1 -deficient malignant pleural mesothelioma mouse models."
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"EZH2 inhibitor tazemetostat have been proven effective in patients with relapsed or refractory, BAP1-inactivated malignant pleural mesothelioma in a multicentre, open-label, phase 2 study (Zauderer et al., 2022)."
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"Loss of BAP1 and MTAP can support the diagnosis of mesothelioma versus benign mesothelial proliferation: however, morphology (with an invasive pattern) is still the essential tool to distinguish malignant from benign disease.Molecular analyses: FISH for alterations in CDKN2A and NF2 (as IHC for BAP1 and MTAP) can be used to support the diagnosis of mesothelioma versus benign mesothelial proliferation."
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"However, TG2-179-1 kills both BAP1-insensitive and BAP1-depleted colon cancer cells as well as BAP1-null mesothelioma and ccRCC cells, indicating that TG2-179-1 targets BAP1 as well as other cellular proteins."
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"Although limited by low sample size, the latter observation suggests there may be functional crosstalk between Hippo pathway deregulation and loss of BAP1 , where a combination of both may drive an ag[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Individuals with pathogenic BAP1 variants face an elevated risk of diverse tumors, notably BAP1-inactivated melanocytic nevi/tumors, uveal melanoma, cutaneous melanoma, mesothelioma, renal cell carcinoma, and basal cell carcinoma."
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"Similar triple-knockout mouse models also confirmed that, although Bap1 deletion alone did not induce mesothelioma, Bap1 deletion dramatically accelerated mesothelioma development with the combined disruption of Nf2 and Cdkn2ab (Badhai et al., 2020)."
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"18 BAP-1 loss of expression might support the diagnosis of mesothelioma, both on cytological samples and on small biopsies, and can differentiate MPM from reactive mesothelial proliferations."
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"Based on its interaction with BRCA1, BAP1 has been shown to increase sensitivity to PARP inhibitors in patients with mesothelioma."
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"Thus, Ezh2 deletion or inhibition was shown to abrogate myeloid malignancy and mesothelioma induced by Bap1 loss (LaFave et al. 2015)."
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"Preventive and therapeutic opportunities: targeting BAP1 and/or HMGB1 pathways to diminish the burden of mesothelioma."
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"Truncating mutations in the tumour suppressor gene BAP1 increased susceptibility to developing malignant pleural mesothelioma (MM)."
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"A pilot study of chemotherapy treatment using previously published doses (Badhai et al., 2020), revealed CNP mice to be extremely sensitive to chemotherapy-induced toxicity, requiring reduction of both drugs to half the concentrations used in mesothelioma mouse model driven by triple deletion of Bap1, Cdkn2a and Nf2 (Badhai et al., 2020)."
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"Badhai et al. suggests additional mutations (Nf2 and Cdkn2ab, which are also frequently observed in human mesotheliomas), in combination with BAP1, led to the rapid onset of mesothelioma in 100% of mice and BAP1 deletion alone caused mesotheliomas in 1 out of 20 mutant mice (5%) in the absence of asbestos exposure (Badhai et al., 2020)."
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"Acquired (somatic) BAP1 inactivating mutations in mesothelioma."
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"BAP1 loss induces mitotic defects in mesothelioma cells through BRCA1-dependent and independent mechanisms."
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"We investigated whether loss of BAP1 expression can be used to support a diagnosis of mesothelioma in effusion cytology."
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"Loss of nuclear BAP1 detected by ICC supports the diagnosis of mesothelioma, mainly of the epithelioid subtype (it is very uncommon in sarcomatous and desmoplastic variants)."
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"Approximately 20-40% of MM have deletions or mutations in BAP1 and germline mutations in this gene increase the risk of mesothelioma development."
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"Loss of BAP1 was shown to increase enhancer of zeste homolog 2 (EZH2) levels in a mesothelioma model , and to increase sensitivity to EZH2 inhibition."
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"While the potential link between BAP1 loss—a known driver of mesothelioma—with response to ICI treatments is intriguing, an important caveat is that BAP1 resides at 3p21.1, a chromosomal region that also contains two other genes encoding epigenetic regulators, PBRM1 and SETD2."
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"Germline mutations in BAP1 predispose carriers to the BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by BAP1-inactivated nevi (BINs), uveal melanoma, cutaneous melanoma, mesothelioma, renal cell carcinoma, and other tumors."
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