News - PBRM1 mutation

Somatic mutational landscape reveals mutational signatures and significantly mutated genes of cancer immunotherapeutic outcome and sex disparities. (PubMed, Front Immunol)

Finally, we discovered co-mutated gene pairs and TP53 p.R282W mutations related to treatment outcomes, highlighting their gender-specific differences. This study identified several molecular biomarkers related to cancer immunotherapy outcomes in terms of mutational signatures, molecular subtypes, and mutated genes, and explored their gender-relatedness in order to provide clues and basis for clinical treatment efficacy evaluation and patient selection.

4 days ago

Journal • Tumor mutational burden • IO biomarker

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ATM (ATM serine/threonine kinase) • NOTCH1 (Notch 1) • PBRM1 (Polybromo 1) • ATRX (ATRX Chromatin Remodeler) • RBM10 (RNA Binding Motif Protein 10) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • EP300 (E1A binding protein p300) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • EPHB1 (EPH Receptor B1)

TP53 mutation • PBRM1 mutation

Myoepithelial-Rich Pleomorphic Adenoma With Novel PLAG1 Inversion on Chromosome 8, and LRP1B, PBRM1 and TCF3 Mutations. (PubMed, Cytopathology)

We present the case of a 64-year-old male with a history of prostate cancer and right submandibular gland excision 16 years ago with an unknown previous diagnosis and recent regrowth of his mass in the surgical bed. The tumour showed a predominant spindle cell morphology, cytokeratin-positivity, variable expression of myoepithelial markers in the cytology and surgical pathology specimens, and novel inversion of the chromosome 8, and LRP1B, PBRM1 and TCF3 mutations.

4 days ago

Journal

PBRM1 (Polybromo 1) • LRP1B (LDL Receptor Related Protein 1B) • TCF3 (Transcription Factor 3) • PLAG1 (PLAG1 Zinc Finger)

PBRM1 mutation

Detection of Novel Fusion Events in Gastric Carcinoma Involving the ARHGAP Gene Family (AMP 2024)

Our study documents novel fusions in MSS gastric carcinoma involving the ARHGAP family. Patients with these tumors usually lack eligibility for targeted therapies, such as those directed against HER2 and involving immune checkpoint inhibition, and could ultimately benefit from new treatment avenues modulating RHOA activity as a result of ARHGAP fusions.

9 days ago

Tumor mutational burden • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • CLDN18 (Claudin 18) • PBRM1 (Polybromo 1) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KDM6A (Lysine Demethylase 6A) • RHOA (Ras homolog family member A) • SOX9 (SRY-Box Transcription Factor 9) • ELF3 (E74 Like ETS Transcription Factor 3) • ARHGAP • CDKN1B (Cyclin dependent kinase inhibitor 1B) • CTNND1 (Catenin Delta 1) • ARHGAP42 (Rho GTPase Activating Protein 42)

TMB-H • HER-2 amplification • PBRM1 mutation

MI Tumor Seek™

13d

Analysis of circulating tumor DNA in treatment-naive patients with metastatic renal cell carcinoma (EMUC 2024)

Conclusions To our knowledge, we report the most sensitive analysis in terms of ctDNA detection in mRCC pt compared to published cohorts. Longitudinal ctDNA assessments could help picture disease evolution on therapy and help refine strategies.

13 days ago

Clinical • IO biomarker • Circulating tumor DNA • Metastases

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein) • KDM6A (Lysine Demethylase 6A) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • EP300 (E1A binding protein p300) • STING (stimulator of interferon response cGAMP interactor 1) • KDM5C (Lysine Demethylase 5C)

TP53 mutation • PBRM1 mutation

FoundationOne® Liquid CDx

Hepatoid thymic carcinoma in a polycythemia vera patient treated with ropeginterferon Alfa-2b: Clinical, histopathological and molecular correlates. (PubMed, Pathol Res Pract)

Whole exome sequencing revealed loss of function mutations in TP53, STK11, PBRM1, SMAD3, FN1, NTRK1, and FANCD2, as well as gain of function mutations in MTOR, BCL11A and COL1A1, along with amplification of CCND3 and MDM2. This mutational landscape halfway between thymic carcinoma (TP53, PBRM1) and hepatoid variant carcinoma of other sites (STK11) suggests that, at some point during carcinogenesis, a switch occurred from an epithelial thymic phenotype to a hepatoid-like one.

1 month ago

Journal

TP53 (Tumor protein P53) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • STK11 (Serine/threonine kinase 11) • mTOR (Mechanistic target of rapamycin kinase) • MDM2 (E3 ubiquitin protein ligase) • PBRM1 (Polybromo 1) • CCND3 (Cyclin D3) • COL1A1 (Collagen Type I Alpha 1 Chain) • FANCD2 (FA Complementation Group D2) • BCL11A (BAF Chromatin Remodeling Complex Subunit BCL11A) • SLC2A1 (Solute Carrier Family 2 Member 1) • SMAD3 (SMAD Family Member 3)

TP53 mutation • STK11 mutation • PBRM1 mutation • MTOR mutation • MDM2 mutation

Besremi (ropeginterferon alfa-2b-njft)

2ms

Evaluation of PD-L1 expression in PBRM1-altered clear cell renal cell carcinoma. (PubMed, Urol Oncol)

Although our study did not establish a correlation between PBRM1 mutations and PD-L1 expression, it demonstrated that the occurrence of PBRM1-altered ccRCC with PD-L1 expression is not uncommon. Therefore, the presence of PBRM1 alterations may challenge the use of PD-L1 IHC as a predictive marker for PD-L1 blockade in ccRCC.

2 months ago

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

PD-L1 (Programmed death ligand 1) • PBRM1 (Polybromo 1)

PD-L1 expression • PBRM1 mutation

PD-L1 IHC 22C3 pharmDx

2ms

Differences in mutations across tumour sizes in clear-cell renal cell carcinoma. (PubMed, BJU Int)

Large and small ccRCCs are genomically different. Aggressive mutations, namely, SETD2, BAP1, and CDKN2A loss, are rarely observed in small ccRCCs and are observed more frequently in larger tumours. However, when present in tumours ≤7 cm, SETD2 mutations and CDKN2A loss were still independently associated with invasive disease, metastasis, worse survival, and recurrence after resection, after controlling for size.

2 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • VHL (von Hippel-Lindau tumor suppressor) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

CDKN2A mutation • PBRM1 mutation • BAP1 mutation • VHL mutation • SETD2 mutation

2ms

Targeted Therapy with Polymeric Nanoparticles in PBRM1-Mutant Biliary Tract Cancers: Harnessing DNA Damage Repair Mechanisms. (PubMed, Crit Rev Oncol Hematol)

In preclinical studies, pharmacokinetic profile of this nanoparticle was encouraging and supported its ability to achieve extended circulation time with high drug accumulation in tumor. The review also highlights potential of Pou3F3:I54N to expedite bioassays for patient selection in BTC targeted therapies.

2 months ago

Review • Journal

PBRM1 (Polybromo 1)

PBRM1 mutation

2ms

A Scoping Review of Population Diversity in the Common Genomic Aberrations of Clear Cell Renal Cell Carcinoma. (PubMed, Oncology)

Studying the genetic aberrations that frequently occur in different regions gives insight into what current research lacks. When more genomic landscape research arises, precision therapy, risk calculators, and artificial intelligence may help better prognosticate and individualize treatment for those at risk for ccRCC. Provided the scarcity of existing data, and the rising prevalence of ccRCC, more studies must be conducted at the clinical level.

2 months ago

Review • Journal

mTOR (Mechanistic target of rapamycin kinase) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • KDM5C (Lysine Demethylase 5C)

PBRM1 mutation • MTOR mutation

6ms

Molecular characteristics of early-onset compared with late-onset colorectal cancer: A case controlled study. (PubMed, Int J Surg)

This study revealed a significantly higher MSI-H distribution rate in early-onset colorectal cancer, and EOCRC exhibits a distinct mutational signature coupled with higher PD-L1 expression. These findings hold promise in guiding personalized therapeutic strategies for improved disease management in EOCRC patients.

6 months ago

Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • LRP1B (LDL Receptor Related Protein 1B) • RNF43 (Ring Finger Protein 43) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • FAT1 (FAT atypical cadherin 1) • CASP8 (Caspase 8) • FANCI (FA Complementation Group I) • KMT2B (Lysine Methyltransferase 2B) • DPYD (Dihydropyrimidine Dehydrogenase)

PD-L1 expression • MSI-H/dMMR • ATM mutation • ARID1A mutation • PBRM1 mutation • RNF43 mutation • KMT2B mutation • FANCI mutation

7ms

The immune response-related genomic alterations in patients with malignant melanoma. (PubMed, Medicine (Baltimore))

In contrast, FAT1, ATM, BRCA2, LRP1B, and PBRM1 mutations only occurred frequently in patients with DCB, irrespective of PD-L1 expression status. Our study explored molecular signatures of melanoma patients who respond to ICIs treatment and identified a series of mutated genes that might serve as predictive biomarker for ICIs responses in melanoma.

7 months ago

Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • BRCA2 (Breast cancer 2, early onset) • NF1 (Neurofibromin 1) • PBRM1 (Polybromo 1) • LRP1B (LDL Receptor Related Protein 1B) • FAT1 (FAT atypical cadherin 1)

PD-L1 expression • BRAF mutation • NF1 mutation • RAS mutation • PBRM1 mutation

7ms

Efficacy of pembrolizumab and biomarker analysis in patients with WGS-based intermediate to high tumor mutational load: results from the Drug Rediscovery Protocol. (PubMed, Clin Cancer Res)

While in cohort A pembrolizumab lacked activity, cohort B and cohort C met the study's primary endpoint. Further research is warranted to refine selection of patients with tumors harboring lower TMLs and may benefit from a focus on innate immunity.

7 months ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker

TMB (Tumor Mutational Burden) • PBRM1 (Polybromo 1) • MICA (MHC Class I Polypeptide-Related Sequence A) • MICB (MHC Class I Polypeptide-Related Sequence B)

PBRM1 mutation

Keytruda (pembrolizumab)

7ms

Dual-loss of PBRM1 and RAD51 identifies hyper-sensitive subset patients to immunotherapy in clear cell renal cell carcinoma. (PubMed, Cancer Immunol Immunother)

PBRM1 and RAD51 dual-loss ccRCC indicates superior responses to immunotherapy. Dual-loss ccRCC harbors an immune-desert microenvironment but enriched with M1 macrophages. Dual-loss ccRCC is susceptible to defective homologous recombination but possesses high chromosomal stability.

7 months ago

Journal • IO biomarker

HRD (Homologous Recombination Deficiency) • PBRM1 (Polybromo 1) • RAD51 (RAD51 Homolog A)

HRD • PBRM1 mutation • RAD51 mutation

8ms

NIRADO: Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (clinicaltrials.gov)

P2, N=51, Suspended, Gustave Roussy, Cancer Campus, Grand Paris | N=112 --> 51 | Trial completion date: Mar 2027 --> Dec 2027 | Recruiting --> Suspended | Trial primary completion date: Mar 2024 --> Dec 2024

8 months ago

Enrollment change • Trial completion date • Trial suspension • Trial primary completion date • Pan tumor

HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • ARID2 (AT-Rich Interaction Domain 2) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)

HER-2 positive • HER-2 amplification • DDR • PBRM1 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • NBN mutation • DRD

Zejula (niraparib) • Jemperli (dostarlimab-gxly)

9ms

Genomic characterization of recurrent uRCC tumors (AUA 2024)

uRCC demonstrates an aggressive disease course with 55% of patients recurring. We identified genomic alterations correlating with recurrence, which may help select patients for treatment intensification, though confirmatory studies are required.

9 months ago

Tumor mutational burden

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

TMB-H • PBRM1 mutation • BAP1 mutation

MSK-IMPACT

9ms

Cancer-associated Polybromo-1 bromodomain 4 missense variants variably impact bromodomain ligand binding and cell growth suppression. (PubMed, J Biol Chem)

Our results demonstrate the effectiveness of identifying the unique impacts of individual PBRM1-BD4 missense variants on protein structure and function, based on affected residue location within the bromodomain. This knowledge provides a foundation for drawing correlations between specific cancer-associated PBRM1 missense variants and distinct alterations in PBRM1 function, informing future cancer personalized medicine approaches.

9 months ago

Journal

PBRM1 (Polybromo 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)

PBRM1 mutation

9ms

PBRM1 presents a potential ctDNA marker to monitor response to neoadjuvant chemotherapy in cervical cancer. (PubMed, iScience)

In vitro, PBRM1 knockdown promoted resistance to cisplatin through boosting STAT3 signaling in cervical cancer cells, while it sensitized tumor cells to poly-ADP-ribose-polymerase inhibitor olaparib. These findings suggest that mutant PBRM1 is a potential ctDNA marker of emerging resistance to NACT and of increased sensitivity to olaparib, which warrants further clinical validation.

9 months ago

Journal • PARP Biomarker • Circulating tumor DNA

ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • PBRM1 (Polybromo 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

PBRM1 mutation • ROS1 mutation • SETD2 mutation

Lynparza (olaparib) • cisplatin

9ms

PBRM1 loss is associated with increased sensitivity to MCL1 and CDK9 inhibition in clear cell renal cancer. (PubMed, Front Oncol)

Increased MCL1 activity has been described as a resistance mechanism to Sunitinib and Everolimus, two approved agents for ccRCC. PRT2527, a potent CDK9 inhibitor which depletes MCL1, was similarly efficacious in monotherapy and in combination with Sunitinib in PBRM1-loss cells. Taken together, these findings suggest PBRM1 loss is associated with MCL1i sensitivity in ccRCC and provide rationale for the evaluation of PRT1419 and PRT2527 for the treatment for PBRM1-deficient ccRCC.

9 months ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • PBRM1 (Polybromo 1)

PBRM1 mutation

sunitinib • everolimus • PRT1419 • PRT2527

10ms

Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma. (PubMed, BMC Med)

MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS.

10 months ago

Journal • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • KMT2D (Lysine Methyltransferase 2D) • RNF43 (Ring Finger Protein 43) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • ACVR2A (Activin A Receptor Type 2A)

PD-L1 expression • TMB-H • MSI-H/dMMR • ARID1A mutation • PBRM1 mutation • RNF43 mutation • PD-L1 expression + MSI-H/dMMR

10ms

Genetic alterations in thyroid cancer mediating both resistance to BRAF inhibition and anaplastic transformation. (PubMed, Oncotarget)

Transition to an immune-suppressed state is another correlate of BRAF inhibitor resistance and tumor dedifferentiation, suggesting a possible role for concurrent targeted therapy with immunotherapy. Investigations into combined targeted and immunotherapy are ongoing, but early results with checkpoint inhibitors, viral therapies, and CAR T-cells suggest enhanced anti-tumor immune activity with these combinations.

10 months ago

Journal • IO biomarker

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • mTOR (Mechanistic target of rapamycin kinase) • PBRM1 (Polybromo 1) • NF2 (Neurofibromin 2) • JAK1 (Janus Kinase 1) • ARID2 (AT-Rich Interaction Domain 2) • PI3K (Phosphoinositide 3-kinases) • RASA1 (RAS P21 Protein Activator 1)

BRAF V600E • PIK3CA mutation • BRAF V600 • PBRM1 mutation • MTOR mutation

10ms

Chromosome 3p gene alterations as biomarkers for immunocombinations in metastatic renal cell carcinoma: A hypothesis-generating analysis. (PubMed, Pathol Res Pract)

Our data shows a possible negative predictive role of SETD2 GA for ICI-based therapy in RCC. Concomitant VHL and PBRM1 GA could act as a predictor for ICI/TKI efficacy. Our hypothesis-generating analysis highlights the need of an integrated evaluation of these genes as promising biomarkers in RCC. Further larger studies are required.

10 months ago

Journal • IO biomarker • Metastases

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • NF2 (Neurofibromin 2) • VHL (von Hippel-Lindau tumor suppressor) • TSC2 (TSC complex subunit 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • TSC1 (TSC complex subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • KDM5C (Lysine Demethylase 5C)

PBRM1 mutation • VHL mutation • SETD2 mutation

11ms

Effects of Purine Metabolism-Related LINC01671 on Tumor Heterogeneity in Kidney Renal Clear Cell Carcinoma. (PubMed, Front Biosci (Landmark Ed))

LINC01671 may be a novel prognostic marker with important therapeutic value for KIRC.

11 months ago

Journal

TP53 (Tumor protein P53) • PBRM1 (Polybromo 1) • CHD4 (Chromodomain Helicase DNA Binding Protein 4) • XIRP2 (Xin Actin Binding Repeat Containing 2) • ABCC6 (ATP Binding Cassette Subfamily C Member 6) • PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin)

TP53 mutation • PBRM1 mutation • VHL mutation

11ms

Multi-omics integration identifies cell-state-specific repression by PBRM1-PIAS1 cooperation. (PubMed, Cell Genom)

Furthermore, SUMOylation contributes to PBRM1's repressive function in progenitor maintenance. Thus, our findings highlight PBRM1's cell-state-specific regulatory roles influenced by its protein interactome despite its stable chromatin binding.

11 months ago

Journal

PBRM1 (Polybromo 1) • PIAS4 (Protein Inhibitor Of Activated STAT 4)

PBRM1 mutation

11ms

An incidental finding of a high-grade glioma with pleomorphic and pseudopapillary features (HPAP) with PBRM1 mutation. (PubMed, J Neuropathol Exp Neurol)

No abstract available

11 months ago

Journal

PBRM1 (Polybromo 1)

PBRM1 mutation

11ms

Impact of Mutations in Subunit Genes of the Mammalian SWI/SNF Complex on Immunological Tumor Microenvironment. (PubMed, Cancer Genomics Proteomics)

These results suggest that immune tumor microenvironment status, such as mature B cell recruitment featuring the TLS gene signature and immune activation mediated by cancer signal down-regulation, might contribute to the classification of SMARCA4 gene-mutated tumors as immune checkpoint blockade therapy-sensitive target tumors.

11 months ago

Journal • IO biomarker

CD20 (Membrane Spanning 4-Domains A1) • PBRM1 (Polybromo 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CD38 (CD38 Molecule) • ARID2 (AT-Rich Interaction Domain 2) • CCR7 (Chemokine (C-C motif) receptor 7) • CD27 (CD27 Molecule) • AURKB (Aurora Kinase B) • IRF4 (Interferon regulatory factor 4) • CD40LG (CD40 ligand)

PBRM1 mutation • SMARCA4 mutation • TLS gene signature

11ms

The immune characteristic analysis of BAP1 mutated clear cell renal cell carcinoma. (ASCO-GU 2024)

This study found that BAP1 and cytokines, cAMP pathway and immune inflammation-related pathways were significantly enriched at the transcriptome level. IHC results suggested that LAG3 was more highly expressed in patients with BAP1 mutation. Clinical treatment analysis found that PD-1 inhibitor-based immune combination therapy is not effective for patients with BAP1 mutations.

11 months ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • LAG3 (Lymphocyte Activating 3) • CD4 (CD4 Molecule)

PD-L1 expression • PBRM1 mutation • BAP1 mutation • CD8 expression • LAG3 expression • CD4 expression

11ms

Fanconi anemia complementation group C (FANCC) gene association with hereditary and sporadic renal tumors (RT). (ASCO-GU 2024)

Somatic and germline mutations in FANCC occur in an exceedingly small subset of clinically advanced RT but at similar rate to other cancers. RT with inactivated FANCC do not appear to have a different GA landscape from RT with wild-type FANCC. The high frequency of predicted germline status during somatic testing with FANCC alterations suggests the importance of further workup with confirmatory germline testing as it may affect counseling for other family members.

11 months ago

Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • DRD (DNA Repair Deficiency) • FANCC (FA Complementation Group C)

PD-L1 expression • TP53 mutation • MSI-H/dMMR • PTEN mutation • ARID1A mutation • DDR • PBRM1 mutation • VHL mutation • DRD

FoundationOne® CDx • PD-L1 IHC 22C3 pharmDx

12ms

Genomic and immune landscape of biliary tract cancers with ARID1A, PBRM1, and BAP1 alterations. (ASCO-GI 2024)

This is the largest known data set exploring the genomic and immune landscape of BTC with ARID1A, PBRM1 and BAP1 alterations. Macrophages were the dominant immune cell TME and may be a target of interest. Co-alteration profile is distinct between ARID1A- vs PBRM1- and/or BAP1-altered BTC.

12 months ago

Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • CD8 (cluster of differentiation 8) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • SMAD4 (SMAD family member 4) • CD4 (CD4 Molecule) • ARID2 (AT-Rich Interaction Domain 2)

MSI-H/dMMR • PBRM1 mutation • BAP1 mutation

Tempus xT Assay • Tempus xR

12ms

PBRM1 mutation and WDR72 expression as potential combinatorial biomarker for predicting the response to Nivolumab in patients with ccRCC: a tumor marker prognostic study. (PubMed, Aging (Albany NY))

The present study indicated that high expression of WDR72 may indicate a good prognosis of patients treated with Nivolumab and WDR72 expression combined with PBRM1 mutation could be more persuasive to predict the response for ICT in ccRCC patients.

12 months ago

Journal • PD(L)-1 Biomarker

CD8 (cluster of differentiation 8) • PBRM1 (Polybromo 1) • FOXP3 (Forkhead Box P3) • CPT1A (Carnitine Palmitoyltransferase 1A)

PBRM1 mutation • FOXP3 expression

Opdivo (nivolumab)

12ms

Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell Carcinoma. (PubMed, Int J Mol Sci)

an increased incidence of KDM5C mutations, which, in common with increased PBRM1 alterations, is also associated with a favourable outcome; and 5. angiogenetic biomarkers are increased in tumour tissue, while inflammatory biomarkers are decreased, which explains the good response to TKI therapy and lack of sensitivity to IT.

12 months ago

Review • Journal

PBRM1 (Polybromo 1) • KDM5C (Lysine Demethylase 5C)

PBRM1 mutation • KDM5C mutation

12ms

Testing the Combination of Two Anti-cancer Drugs, Peposertib (M3814) and M1774 for Advanced Solid Tumors (clinicaltrials.gov)

P1, N=66, Recruiting, National Cancer Institute (NCI) | Phase classification: P1b --> P1 | Initiation date: Nov 2023 --> Feb 2024

12 months ago

Phase classification • Trial initiation date

ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • PBRM1 (Polybromo 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • ARID1B (AT-Rich Interaction Domain 1B) • ARID2 (AT-Rich Interaction Domain 2) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)

ATM mutation • ARID1A mutation • CCNE1 amplification • PBRM1 mutation • CCNE1 mutation

peposertib (M3814) • tuvusertib (M1774)

12ms

Genomic profiling of tissue and blood predicts survival outcomes in patients with resected pleural mesothelioma. (PubMed, Eur J Cancer)

Tissue TMB and MAF, blood TMB, and specific mutations correlated with outcomes in patients with resected PM and should be further studied to validate their role as prognostic biomarkers and potentially predictive factors for combinations with immune-checkpoint inhibitors. This suggest that molecular profiling could identify longer survivors in patients with resected PM.

12 months ago

Journal • Tumor mutational burden

TMB (Tumor Mutational Burden) • PBRM1 (Polybromo 1) • KMT2C (Lysine Methyltransferase 2C) • LIFR (LIF Receptor Subunit Alpha) • EPHB1 (EPH Receptor B1) • PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin)

PBRM1 mutation

1year

Unveiling the immunogenomic landscape of cholangiocarcinoma: Identifying new prognostic markers and therapeutic targets based on CCL5 expression. (PubMed, J Gene Med)

The present study provides an intricate depiction of the immunogenomic landscape of CCA based on CCL5 expression, thereby paving the way for novel immunotherapy strategies and prognostic assessment.

1 year ago

Journal • IO biomarker

PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • CCL5 (Chemokine (C-C motif) ligand 5)

PBRM1 mutation • BAP1 mutation

1year

A hypothesis generating analysis of the role of chromosome 3p-related genes as predictors for immunocombinations in metastatic renal cell carcinoma (mRCC) (EMUC 2023)

Our hypothesis-generating data highlights the need of an integrated evaluation of 3p-related genes as promising biomarkers in RCC. Further and wider studies are required.

1 year ago

IO biomarker • Metastases

PBRM1 mutation • VHL mutation • SETD2 mutation

1year

Mutational profile of primary clear cell renal cell carcinoma predicts recurrence and potential selection for adjuvant therapy (EMUC 2023)

Presence of somatic “non-VHL” mutations in PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, or PTEN genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01). Conclusions These findings support the prognostic value of “non-VHL” mutations including PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, and PTEN in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant therapy.

1 year ago

Clinical

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • mTOR (Mechanistic target of rapamycin kinase) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • NF2 (Neurofibromin 2) • VHL (von Hippel-Lindau tumor suppressor) • TSC2 (TSC complex subunit 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • TSC1 (TSC complex subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • KDM5C (Lysine Demethylase 5C)

ATM mutation • PTEN mutation • PBRM1 mutation • BAP1 mutation • VHL mutation • TSC1 mutation • TSC2 mutation • MTOR mutation • SETD2 mutation

1year

MUC1-C INTEGRATES CHRONIC ACTIVATION OF INTERFERON PATHWAYS WITH CHROMATIN REMODELING IN TREATMENT RESISTANCE OF TRIPLE-NEGATIVE BREAST CANCER (SABCS 2023)

In support of these results, targeting MUC1-C in wild-type BRCA1/2 TNBC cells enhanced carboplatin-induced DNA damage and loss of self- renewal capacity. In addition, MUC1-C was necessary for DNA damage resistance, self-renewal and tumorigenicity of olaparib-resistant BRCA1-mutant TNBC cells...As one example, an allogeneic anti-MUC1-C CAR T cell using MAb 3D1 sequences is undergoing Phase I evaluation for the treatment of MUC1-C-expressing cancers (NCT05239143: P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects with Advanced or Metastatic Solid Tumors). In addition, anti-MUC1-C huMAb3D1-MMAE ADCs are under development by the NCI NExT Program for IND-enabling studies and performing early phase clinical trials in patients with TNBC.

1 year ago

BRCA Biomarker • PARP Biomarker • IO biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PBRM1 (Polybromo 1) • MUC1 (Mucin 1) • IDO1 (Indoleamine 2,3-dioxygenase 1) • STING (stimulator of interferon response cGAMP interactor 1) • IRF1 (Interferon Regulatory Factor 1) • STAT1 (Signal Transducer And Activator Of Transcription 1) • IFIH1 (Interferon Induced With Helicase C Domain 1)

BRCA1 mutation • BRCA wild-type • PBRM1 mutation • MUC1 expression • IRF1 expression

Lynparza (olaparib) • carboplatin • P-MUC1C-ALLO1

1year

Genomic Analysis in the Categorization of Poorly Differentiated Primary Liver Carcinomas. (PubMed, Am J Surg Pathol)

Though not specific, these genomic alterations can provide valuable diagnostic clues in selected morphologically and immunohistochemically unclassifiable cases. Given the important differences in management between HCC and iCCA, routine use of genomic analysis in diagnostically challenging settings should be considered.

1 year ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1)

HER-2 mutation • IDH1 mutation • FGFR2 mutation • FGFR2 fusion • PBRM1 mutation • BAP1 mutation

1year

The stratification and prognostic importance of molecular and immune landscapes in clear cell renal cell carcinoma. (PubMed, Front Oncol)

Finally, we have discovered the function of DKK1 in facilitating cell death in ccRCC, presenting an additional possibility for therapeutic intervention. The results of our study suggest the possibility of incorporating molecular information into clinical prediction, which could lead to personalized treatment approaches in ccRCC.

1 year ago

Journal • IO biomarker

PBRM1 (Polybromo 1) • DKK1 (dickkopf WNT signaling pathway inhibitor 1)

PBRM1 mutation

1year

Testing the Combination of Two Anti-cancer Drugs, Peposertib (M3814) and M1774 for Advanced Solid Tumors (clinicaltrials.gov)

P1b, N=66, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting | Initiation date: May 2023 --> Nov 2023

1 year ago

Enrollment open • Trial initiation date • Combination therapy • Metastases

ATM mutation • ARID1A mutation • CCNE1 amplification • PBRM1 mutation • CCNE1 mutation

peposertib (M3814) • tuvusertib (M1774)

1year

The crosstalk between PBRM1 loss and tumor immune microenvironment (TIME) of clear cell renal cell carcinoma (ccRCC): A possible interconnection to immunotherapy response (ESMO Asia 2023)

In addition, PBRM1 loss was correlated with a superior response to nivolumab in a cohort of 35 patients (fold change = 58.7 and P = .0123). Conclusions PBRM1 Loss induces global transcription alternations that impact many immunological processes. Such phenomena could be associated with the positive correlation to immunotherapy response in ccRCC.

1 year ago

PD(L)-1 Biomarker • IO biomarker

CD8 (cluster of differentiation 8) • PBRM1 (Polybromo 1) • TNFA (Tumor Necrosis Factor-Alpha)

PBRM1 mutation

Opdivo (nivolumab)

1year

Genomics-based characterization and personalized treatment in pleural and peritoneal mesothelioma (DGHO 2023)

Our findings suggest efficacy of personalized therapies in MPM. They underscore the need for further clinical investigation into HR deficiency in MPM beyond BAP1 alterations.

1 year ago

Tumor mutational burden • BRCA Biomarker • IO biomarker

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • NF1 (Neurofibromin 1) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • NF2 (Neurofibromin 2) • B2M (Beta-2-microglobulin) • CHEK2 (Checkpoint kinase 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • ARID2 (AT-Rich Interaction Domain 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • XPA (XPA, DNA Damage Recognition And Repair Factor) • SETDB1 (SET Domain Bifurcated Histone Lysine Methyltransferase 1) • DDX3X (DEAD-Box Helicase 3 X-Linked)

PBRM1 mutation • BAP1 mutation