News - BAP1 deletion - LARVOL VERI

23d

BAP1 inactivation promotes lactate production by leveraging the subcellular localization of LDHA in melanoma. (PubMed, Cell Death Discov)

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.

23 days ago

Journal • BRCA Biomarker

LDHA (Lactate dehydrogenase A) • BAP1 (BRCA1 Associated Protein 1)

BAP1 mutation • BAP1 deletion

3ms

BAP1 regulates HSF1 activity and cancer immunity in pancreatic cancer. (PubMed, J Exp Clin Cancer Res)

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.

3 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BAP1 (BRCA1 Associated Protein 1) • PDX1 (Pancreatic And Duodenal Homeobox 1) • SIRT1 (Sirtuin 1) • HSF1 (Heat Shock Transcription Factor 1)

KRAS G12D • KRAS G12 • BAP1 deletion

10ms

BAP31 Promotes Adhesion Between Endothelial Cells and Macrophages Through the NF-κB Signaling Pathway in Sepsis. (PubMed, J Inflamm Res)

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.

10 months ago

Journal • IO biomarker

MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BAP1 (BRCA1 Associated Protein 1) • TNFA (Tumor Necrosis Factor-Alpha) • ICAM1 (Intercellular adhesion molecule 1) • TLR4 (Toll Like Receptor 4) • IL1B (Interleukin 1, beta) • NFKBIA (NFKB Inhibitor Alpha 2) • VCAM1 (Vascular Cell Adhesion Molecule 1) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule) • TRAF6 (TNF Receptor Associated Factor 6)

BAP1 deletion

1year

Multi-omics comparison of malignant and normal uveal melanocytes reveals molecular features of uveal melanoma. (PubMed, Cell Rep)

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.

1 year ago

Journal

BAP1 (BRCA1 Associated Protein 1) • PRAME (Preferentially Expressed Antigen In Melanoma)

BAP1 deletion

over1year

RITA selectively inhibits proliferation of BAP1-deficient cutaneous melanoma cells in vitro (PubMed, Nan Fang Yi Ke Da Xue Xue Bao)

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.

over 1 year ago

Preclinical • Journal

BAP1 (BRCA1 Associated Protein 1)

BAP1 mutation • BAP1 deletion • TP53 expression

RITA

2years

Mullerian adenosarcoma: clinicopathologic and molecular characterization highlighting recurrent BAP1 loss and distinctive features of high-grade tumors. (PubMed, Mod Pathol)

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.

2 years ago

Journal

ER (Estrogen receptor) • TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • TERT (Telomerase Reverse Transcriptase) • CCNE1 (Cyclin E1) • MDM2 (E3 ubiquitin protein ligase) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • ATRX (ATRX Chromatin Remodeler) • DICER1 (Dicer 1 Ribonuclease III) • NCOA3 (Nuclear Receptor Coactivator 3)

TP53 mutation • ARID1A mutation • CCNE1 amplification • BAP1 mutation • ATRX mutation • BAP1 deletion • TERT mutation • ATRX deletion • TERT promoter mutation

over2years

BAP1-defficient breast cancer in a patient with BAP1 cancer syndrome. (PubMed, Breast Cancer)

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.

over 2 years ago

Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • BAP1 (BRCA1 Associated Protein 1)

PD-L1 expression • TMB-L • BAP1 deletion

Tecentriq (atezolizumab) • albumin-bound paclitaxel

3years

Co-occurrence of BAP1 and SF3B1 mutations in uveal melanoma induces cellular senescence. (PubMed, Mol Oncol)

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.

3 years ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • SF3B1 (Splicing Factor 3b Subunit 1) • BAP1 (BRCA1 Associated Protein 1)

TP53 mutation • BRCA1 mutation • TP53 deletion • SF3B1 mutation • BAP1 mutation • BAP1 deletion • TP53 expression

3years

BAP1 methylation: a prognostic marker of uveal melanoma metastasis. (PubMed, NPJ Precis Oncol)

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.

3 years ago

Journal

BAP1 (BRCA1 Associated Protein 1)

BAP1 deletion

over3years

[VIRTUAL] Histopathological outlook for BAP1 tumour predisposition syn- drome - case report (ECP 2021)

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.

over 3 years ago

Clinical • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BAP1 (BRCA1 Associated Protein 1) • BRCA (Breast cancer early onset)

BRCA1 mutation • BAP1 mutation • BAP1 deletion • BRCA mutation

almost4years

Alterations in BAP1 are Associated with Cisplatin Resistance Through Inhibition of Apoptosis in Malignant Pleural Mesothelioma (MPM). (PubMed, Clin Cancer Res)

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.

almost 4 years ago

Journal

BAP1 (BRCA1 Associated Protein 1) • E2F1 (E2F transcription factor 1)

BAP1 mutation • BAP1 deletion

cisplatin • pemetrexed

almost4years

[VIRTUAL] Expressions of Biomarkers of Malignant Pleural Mesothelioma at Pham Ngoc Thach Hospital, Vietnam in 5 Years From 2015-2019 (IASLC-TTLC 2021)

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.

almost 4 years ago

Clinical • PD(L)-1 Biomarker • IO biomarker

BAP1 (BRCA1 Associated Protein 1) • WT1 (WT1 Transcription Factor) • XIAP (X-Linked Inhibitor Of Apoptosis)

PD-L1 expression • BAP1 deletion

PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay

almost4years

Bioinformatic Analysis of Differentially Expressed Genes and Screening of Hub Genes in Uveal Melanoma Cells with BRCA1-Associated Protein 1 Related Protein 1 Depletion. (PubMed, J Biomed Nanotechnol)

A total of 269 up-regulated and 807 down-regulated genes were identified from the combined GSE110193 and GSE48863 data sets...The potential targets of BAP1 include CXCL8, COL5A3, COL11A1, and COL12A1. It is believed that BAP1 regulates UVM cell adhesion through these four genes and ultimately regulates tumor development and migration.

almost 4 years ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BAP1 (BRCA1 Associated Protein 1) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • COL1A1 (Collagen Type I Alpha 1 Chain)

BAP1 deletion • BRCA1 expression

Zydelig (idelalisib)

almost4years

The value of BAP1 immunocytochemistry and CDKN2A fluorescence in situ hybridization in diagnosis of serous effusion malignant mesothelioma and an analysis of the association between degree of cell atypia and the results of two auxiliary methods. (PubMed, Pol J Pathol)

BAP1 ICC and CDKN2A FISH are useful methods to differentiate MM from BMP. The cell atypia of MM with BAP1 expression was more obvious than MM with BAP1 nonexpression.

almost 4 years ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1)

CDKN2A deletion • BAP1 deletion

almost4years

BAP1 deletion abrogates growth and metastasis of murine cutaneous melanoma. (PubMed, Melanoma Res)

Transcriptomic characterization of BAP1 deletion reveals multiple deregulated cellular functions including extracellular matrix-receptor interaction and MAPK signaling pathway which may contribute to BAP1's effect on metastasis and proliferation. Our findings indicate that BAP1 could be a potential therapeutic target for CM.

almost 4 years ago

Preclinical • Journal • BRCA Biomarker

BAP1 (BRCA1 Associated Protein 1) • BRCA (Breast cancer early onset)

BAP1 mutation • BAP1 deletion • BRCA mutation

4years

Biomarker-guided targeted and immunotherapies in malignant pleural mesothelioma. (PubMed, Ther Adv Med Oncol)

In this review, we provide an up-to-date overview of recent advances in MPM by focusing on new stratifications of tumor subgroups, specific vulnerabilities associated with functional loss of TSGs and other biomarkers, and potential clinical implications. The molecularly based subdivisions not only deepen our understanding of MPM pathobiology, but more importantly, they may raise unprecedented new hopes for personalized treatment of MPM patients with biomarker-guided targeted and immunotherapies.

4 years ago

Review • Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion • BAP1 deletion

4years

Association of Partial Chromosome 3 Deletion in Uveal Melanomas With Metastasis-Free Survival. (PubMed, JAMA Ophthalmol)

These findings suggest that partial deletion of chromosome 3 encompassing the BAP1 locus is associated with poor prognosis. A cytogenetic classification of UMs could be proposed based on the status of the BAP1 locus instead of the chromosome 3 locus, while also taking chromosome 8q into account.

4 years ago

Journal

BRCA1 (Breast cancer 1, early onset) • BAP1 (BRCA1 Associated Protein 1)

BAP1 deletion

4years

Genomic Profiling of Multifocal Intrahepatic Cholangiocarcinoma Reveals Intraindividual Concordance of Genetic Alterations. (PubMed, Carcinogenesis)

In this cohort of multifocal IHC, genomic profiles were concordant across all tumors in each patient, suggesting a common progenitor cell origin, regardless of the location of tumors in the liver. The decision to perform surgery should not be based upon a perceived distinction between IM and SN.

4 years ago

Clinical • Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BAP1 (BRCA1 Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • MSH6 (MutS homolog 6) • CHEK1 (Checkpoint kinase 1)

BAP1 mutation • BAP1 deletion

4years

Sarcomatoid Mesothelioma: A CDKN2A molecular analysis of 53 cases with immunohistochemical correlation with BAP1. (PubMed, Pathol Res Pract)

Our findings showed that even though the use of BAP1 and p16 are important tools in the diagnosis of mesothelioma, a proportion of cases still remains negative with approximately 30 % of the cases in which the concordance of BAP1 loss and p16 homozygous deletion will not be present. We consider that the final diagnosis of mesothelioma is best accomplished by a global interpretation of clinical, radiographic, and pathological features including immunohistochemistry and molecular studies.

4 years ago

Clinical • Journal • BRCA Biomarker

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1) • BRCA (Breast cancer early onset)

CDKN2A deletion • BAP1 deletion • BRCA deletion

4years

[VIRTUAL] Clinicopathologic Characteristics of Sarcomatoid Mesothelioma (CAP 2020)

The correct diagnosis of sarcomatoid mesothelioma can be challenging. Inclusion of a panel of IHC/FISH markers, including BAP1 and CDKN2A, is necessary. Furthermore, correlation with clinical findings, especially radiology, is important to establish a correct diagnosis.

4 years ago

Clinical

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1) • VIM (Vimentin) • CALR (Calreticulin)

CDKN2A deletion • BAP1 deletion

4years

Whole Exome Sequencing Identifies Candidate Genes Associated with Hereditary Predisposition to Uveal Melanoma. (PubMed, Ophthalmology)

The study provided moderate evidence of gene and disease association of germline mutations in PALB2 and MLH1 with hereditary predisposition to UM. It also identified several other candidate susceptibility genes. The results suggest locus heterogeneity in predisposition to UM. Genetic testing for hereditary predisposition to cancer is warranted in UM patients with strong personal or family history of cancers, or both.

4 years ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • CHEK2 (Checkpoint kinase 2) • CTNNA1 (Catenin Alpha 1)

PALB2 mutation • BAP1 mutation • MLH1 mutation • BAP1 deletion

over4years

Whole exome sequencing reveals BAP1 somatic abnormalities in mesothelioma in situ. (PubMed, Lung Cancer)

Whole exome sequencing confirms that mesothelioma in situ development is associated with BAP1 somatic mutations/deletions, and suggests that BAP1 mutation/deletion represents a very early event in the development of malignant mesothelioma. Whether BAP1 mutation/deletion alone is sufficient to lead to invasive mesothelioma or whether additional genetic alterations are required remains to be determined.

over 4 years ago

Journal

BAP1 (BRCA1 Associated Protein 1)

BAP1 mutation • BAP1 deletion

over4years

BAP1 is a haploinsufficient tumor suppressor linking chronic pancreatitis to pancreatic cancer in mice. (PubMed, Nat Commun)

Heterozygous mice also develop pancreatic cancer suggesting a haploinsufficient tumor suppressor role for BAP1. Mechanistically, BAP1 regulates genomic stability, in a catalytic independent manner, and its loss confers sensitivity to irradiation and platinum-based chemotherapy in pancreatic cancer.

over 4 years ago

Preclinical • Journal • BRCA Biomarker

KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BAP1 (BRCA1 Associated Protein 1)

BAP1 deletion • KRAS expression

over4years

Systematic Analysis of Aberrant Biochemical Networks and Potential Drug Vulnerabilities Induced by Tumor Suppressor Loss in Malignant Pleural Mesothelioma. (PubMed, Cancers (Basel))

Finally, multiple lines of evidence support Dasatinib as a promising therapeutic for LATS2-mutant MPM. Systematic identification of abnormal cellular processes and potential drug vulnerabilities specified by TSG alterations provide a framework for precision oncology in MPM.

over 4 years ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1)

BAP1 mutation • BAP1 deletion • miR-138 underexpression + miR-497 overexpression

dasatinib

over4years

[VIRTUAL] Studying BAP1 in Regulating Glucose Dependency in Renal Cancer: Mechanisms and Preclinical Translation (KCRS-I 2020)

(ii) Clinical impact: Our studies may identify GLUT inhibitors as effective therapies to treat renal cancer patients with BAP1 mutation or deficiency. Funding Mechanism: Idea Development Award - Established Investigator

over 4 years ago

Preclinical

BAP1 (BRCA1 Associated Protein 1)

BAP1 mutation • BAP1 deletion

over4years

Testing for BAP1 loss and CDKN2A/p16 homozygous deletion improves the accurate diagnosis of mesothelial proliferations in effusion cytology. (PubMed, Cancer Cytopathol)

These findings suggest that routine use of BAP1 immunochemistry and p16 FISH as adjunctive tests improves the diagnostic accuracy of cytology specimens and potentially allows an earlier diagnosis of malignant mesothelioma.

over 4 years ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1)

CDKN2A deletion • BAP1 deletion • miR-138 underexpression + miR-497 overexpression

over4years

Inactivation of Bap1 Cooperates with Losses of Nf2 and Cdkn2a to Drive the Development of Pleural Malignant Mesothelioma in Conditional Mouse Models. (PubMed, Cancer Res)

RNA-seq analysis of MMs from triple-CKO mice revealed enrichment of genes transcriptionally regulated by the polycomb repressive complex 2 (PRC2) and others previously implicated in known Bap1-related cellular processes. These data demonstrate that somatic inactivation of Bap1, Nf2, and Cdkn2a results in rapid, aggressive MMs, and that deletion of Bap1 contributes to tumor development, in part, by loss of PRC2-mediated gene repression of tumorigenic target genes and by acquisition of stem-cell potential, suggesting a potential avenue for therapeutic intervention.

over 4 years ago

Preclinical • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1)

CDKN2A deletion • BAP1 mutation • NF2 mutation • BAP1 deletion

over4years

Morphological difference between pleural mesothelioma cells in effusion smears with either BAP1 loss or 9p21 homozygous deletion and reactive mesothelial cells without the gene alterations. (PubMed, Pathol Int)

MPM cells with BAP1 loss or 9p21 HD exhibited significantly more frequent cell-in-cell engulfment, multinucleation, and larger multicellular clusters composed of more than 10 cells than reactive mesothelial cells. In conclusion, MPM cells with BAP1 loss or 9p21 HD share similar cytological features, indicating that the same morphological criteria can be used to detect MPM cells harboring such genetic aberrations.

over 4 years ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BAP1 (BRCA1 Associated Protein 1)

BAP1 deletion

over4years

Diagnosis and characterization of malignant effusions through pleural fluid cytological examination. (PubMed, Curr Opin Pulm Med)

A judicious use of pleural fluid cytologic specimens, which includes immunocytochemistry and molecular testing, eliminates the need for more invasive tissue sampling.

over 4 years ago

Journal • PD(L)-1 Biomarker

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • BAP1 (BRCA1 Associated Protein 1)

BAP1 deletion

over4years

HEG1, BAP1, and MTAP are useful in cytologic diagnosis of malignant mesothelioma with effusion. (PubMed, Diagn Cytopathol)

HEG1 is a good marker for mesothelial differentiation in effusion cytology. HD of CDKN2A is frequently observed in cell blocks from effusions of MMs, and MTAP IHC may act as a surrogate for HD of CDKN2A. Cell block analysis is recommended for effusions of unknown origins with the following IHC with HEG1 and claudin 4 to validate the mesothelial origin, followed by BAP1 and MTAP IHC to confirm malignancy.

over 4 years ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1)

CDKN2A deletion • BAP1 deletion

over4years

Studying BAP1 in Regulating Glucose Dependency in Renal Cancer: Mechanisms and Preclinical Translation (KCRS 2020)

Impact: (i) Fundamental impact: Our proposed study will provide important mechanistic insight into nutrient dependency in renal cancer. (ii) Clinical impact: Our studies may identify GLUT inhibitors as effective therapies to treat renal cancer patients with BAP1 mutation or deficiency.

over 4 years ago

Preclinical

BAP1 (BRCA1 Associated Protein 1)

BAP1 mutation • BAP1 deletion

over4years

Targeted Next-Generation Sequencing of 117 Routine Clinical Samples Provides Further Insights into the Molecular Landscape of Uveal Melanoma. (PubMed, Cancers (Basel))

NGS can simultaneously assess SCNA and mutation data in UM, in a reliable and reproducible way, irrespective of sample type or previous processing. BAP1 and SF3B1 mutations, in addition to 8q copy number, are of added importance when determining UM patient outcome.

over 4 years ago

Clinical • Journal

GNAQ (G Protein Subunit Alpha Q) • SF3B1 (Splicing Factor 3b Subunit 1) • BAP1 (BRCA1 Associated Protein 1) • GNA11 (G Protein Subunit Alpha 11)

TP53 mutation • GNAQ mutation • SF3B1 mutation • BAP1 mutation • BAP1 deletion

over4years

Telomerase reverse transcriptase promoter mutations identify a genomically defined and highly aggressive human pleural mesothelioma subgroup. (PubMed, Clin Cancer Res)

TERT promoter mutations independently predict a dismal course of disease in human MPM. The altered genomic aberration pattern indicates that TERT promoter mutations identify a novel, highly aggressive MPM subtype presumably based on a specific malignant transformation process.

over 4 years ago

Journal

BAP1 (BRCA1 Associated Protein 1)

BAP1 mutation • BAP1 deletion

over4years

Combined deletion of Bap1, Nf2, and Cdkn2ab causes rapid onset of malignant mesothelioma in mice. (PubMed, J Exp Med)

Treatment of BNC tumor-bearing mice with cisplatin and pemetrexed, the current frontline treatment, prolongs survival. This makes the autochthonous mouse model described here very well suited to explore the pathogenesis of MM and validate new treatment regimens for MM, including immunotherapy.

over 4 years ago

Preclinical • Journal

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • BAP1 (BRCA1 Associated Protein 1)

BAP1 deletion

cisplatin • pemetrexed

over4years

Application of immunohistochemistry in diagnosis and management of malignant mesothelioma. (PubMed, Transl Lung Cancer Res)

Some diagnostic markers also have prognostic significance, and PD-L1 immunohistochemistry may predict tumor response to immunotherapy. Application and interpretation of these immnuomarkers should always be guided by clinical history, radiographic findings, and above all histomorphology.

over 4 years ago

Review • Journal • PD(L)-1 Biomarker

PD-L1 (Programmed death ligand 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • EPCAM (Epithelial cell adhesion molecule) • CALR (Calreticulin)

BAP1 deletion

almost5years

[VIRTUAL] A phase II trial of nivolumab in combination with talazoparib in unresectable or metastatic melanoma patients with mutations in BRCA or BRCAness. (ASCO 2020)

The study is currently open and enrolling patients. Research Funding: Pfizer, Internal funding

almost 5 years ago

Clinical • P2 data • Combination therapy • Tumor Mutational Burden • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • CDK4 (Cyclin-dependent kinase 4) • BRCA (Breast cancer early onset) • FANCA (FA Complementation Group A) • ATR (Ataxia telangiectasia and Rad3-related protein) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • HDAC2 (Histone deacetylase 2) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)

PD-L1 expression • ARID1A mutation • BAP1 mutation • BRIP1 mutation • FANCA mutation • BAP1 deletion • RAD50 mutation • BARD1 mutation • BLM mutation • BRCA mutation • NBN mutation • BRCA deletion

Opdivo (nivolumab) • Talzenna (talazoparib)