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Last update 23 Jan 2025

PBRM1

Last update 23 Jan 2025

Basic Info

Synonyms

BAF180, BRG1-associated factor 180, hPB1

+ [6]

Introduction

Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Required for the stability of the SWI/SNF chromatin remodeling complex SWI/SNF-B (PBAF). Acts as a negative regulator of cell proliferation.

Drugs associated with PBRM1

GNE-064

Target

PBRM1 x SMARCA2 x SMARCA4

Mechanism

PBRM1 inhibitors [+2]

Active Org.

Genentech, Inc.

Originator Org.

Genentech, Inc.

Active Indication

Microsatellite Instability cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

AU-15330

Target

PBRM1 x SMARCA2 x SMARCA4

Mechanism

PBRM1 inhibitors [+3]

Active Org.

Aurigene Oncology Ltd. [+1]

Originator Org.

University of Michigan

Active Indication

Acute Myeloid Leukemia [+1]

Inactive Indication

Prostatic Cancer

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

AU-24118

Target

ATPase x PBRM1

Mechanism

ATPase inhibitors [+1]

Active Org.

University of Michigan

Originator Org.

University of Michigan

Active Indication

Prostatic Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PBRM1

100 Translational Medicine associated with PBRM1

0 Patents (Medical) associated with PBRM1

613

Literatures (Medical) associated with PBRM1

01 Feb 2025·Pathology - Research and Practice

Clinicopathologic and genomic characteristics of biliary tract carcinomas with TERT promoter mutations among East Asian population

Article

Author: Kim, Deok Geun ; Kim, Kyoung-Mee ; Hwang, Inwoo ; Kang, So Young ; Jang, Kee-Taek

Telomerase reverse transcriptase gene promoter (TERT) mutations are biomarkers that predict survival and responses to immune checkpoint inhibitors in various malignancies. However, their prevalence and clinicopathologic characteristics in biliary tract carcinomas are largely unknown. We performed a comprehensive genomic profiling of formalin-fixed paraffin-embedded tumor tissue from 485 carcinomas, including intrahepatic (n = 220), perihilar (n = 54), distal biliary tract (n = 110), and gallbladder (n = 101) cancers, using next-generation sequencing. TERT mutations were observed in 50 out of 485 biliary tract cancers (10.3 %) consisting of 39 C228T (78.0 %) and 11 C250T (22.0 %) variants. Among the different anatomic locations, TERT mutations were most frequent in the gallbladder (20.8 %), followed by perihilar (9.3 %), intrahepatic (7.7 %), and distal bile ducts (6.4 %) (p < 0.01). Genetically, TERT mutations were significantly associated with TP53 mutations (p = 0.04), ERBB2 amplification (p < 0.01), and high tumor mutational burdens (TMB) (p < 0.01); moreover, they were negatively correlated with KRAS (p < 0.01), SMAD4 (p = 0.01), and PBRM1 mutations (p = 0.01). In addition, TERT mutations were associated with a poor progression-free survival (PFS, p = 0.01). Specifically, in cases of intrahepatic cholangiocarcinoma, TERT mutations were more frequent in patients with cirrhosis (p = 0.01), hepatitis B virus infection (p = 0.04), and advanced disease stages (p < 0.01). In gallbladder carcinoma, TERT mutations were also associated with poor PFS. In conclusion, TERT mutations in biliary tract carcinomas had unique clinicopathologic and genetic characteristics. Despite its poor PFS, the concomitant presence of ERBB2 amplification and a high TMB indicated a potential for targeted therapy and immunotherapy in this specific subtype.

01 Feb 2025·Molecular Aspects of Medicine

The molecular code of kidney cancer: A path of discovery for gene mutation and precision therapy

Review

Author: Li, Xiaorui ; Wang, Xiaoxi ; Li, Guandu ; Wu, Guangzhen ; Zhang, Xiaoman ; Zheng, Zunwen ; Xie, Deqian ; Jiang, Bowen ; Wang, Shijin

Renal cell carcinoma (RCC) is a malignant tumor with highly heterogeneous and complex molecular mechanisms. Through systematic analysis of TCGA, COSMIC and other databases, 24 mutated genes closely related to RCC were screened, including VHL, PBRM1, BAP1 and SETD2, which play key roles in signaling pathway transduction, chromatin remodeling and DNA repair. The PI3K/AKT/mTOR signaling pathway is particularly important in the pathogenesis of RCC. Mutations in genes such as PIK3CA, MTOR and PTEN are closely associated with metabolic abnormalities and tumor cell proliferation. Clinically, mTOR inhibitors and VEGF-targeted drugs have shown significant efficacy in personalized therapy. Abnormal regulation of metabolic reprogramming, especially glycolysis and glutamine metabolic pathways, provides tumor cells with continuous energy supply and survival advantages, and GLS1 inhibitors have shown promising results in preclinical studies. This paper also explores the potential of immune checkpoint inhibitors in combination with other targeted drugs, as well as the promising application of nanotechnology in drug delivery and targeted therapy. In addition, unique molecular mechanisms are revealed and individualized therapeutic strategies are explored for specific subtypes such as TFE3, TFEB rearrangement type and SDHB mutant type. The review summarizes the common gene mutations in RCC and their molecular mechanisms, emphasizes their important roles in tumor diagnosis, treatment and prognosis, and looks forward to the application prospects of multi-pathway targeted therapy, metabolic targeted therapy, immunotherapy and nanotechnology in RCC treatment, providing theoretical support and clinical guidance for individualized treatment and new drug development.

01 Feb 2025·Pathology - Research and Practice

Tumor infiltrating T-cells and loss of expression of SWI/SNF genes in varying stages of clear cell renal cell carcinoma

Article

Author: Xia, Yan ; O'Neill, Raymond ; Hrizat, Alaa S ; Eberle-Singh, Jaime ; McCue, Peter A ; Yang, Haifeng ; Lin, Ruihe ; Testa, Joseph R ; Uzzo, Robert ; Li, Li

BACKGROUNDPatients with clear cell renal cell carcinoma (ccRCC) metastases face poor prognoses, even with adjuvant therapies. Tumor-infiltrating T-cells and macrophages are critical in targeting tumor cells within the renal microenvironment. Beyond VHL mutations, loss-of-function mutations in SWI/SNF complex genes, including PBRM1, BAP1, ARID1A, SETD2, SMARCA4 (BRG1), and SMARCA2 (BRM), have been implicated in ccRCC progression.DESIGNA tissue microarray of 160 ccRCC cases was analyzed via immunohistochemistry (IHC) for SWI/SNF protein expression and CD4 + /CD8 + T-cell infiltration. Clinical and pathologic features were obtained through electronic medical records. Statistical analyses included one-way ANOVA, two-way ANOVA, Pearson's chi-square and t-tests.RESULTSLoss of SWI/SNF protein expression was observed in PBRM1 (31 %), ARID1A (51 %), SETD2 (14 %), BRG1 (15 %), BRM (38 %), and BAP1 (40 %). T-cell counts varied significantly with stage: CD4 + counts peaked at Stage 3, while CD8 + counts increased through Stage 4 (p < 0.001). Loss of PBRM1 was more frequent in advanced stages (29.4 %, p < 0.001), while BRM and BRG1 losses were more common in earlier stages (p < 0.001, p = 0.006). ARID1A and BRM losses correlated with reduced CD8 + counts (p = 0.016, p = 0.032) and stage-specific CD4 + variations (p < 0.001, p = 0.042).CONCLUSIONLoss of PBRM1, SMARCA2/BRM, and SMARCA4/BRG1 expression is significantly associated with ccRCC progression, with PBRM1 loss prevalent in advanced stages and SMARCA2/BRM and SMARCA4/BRG1 in earlier stages. ARID1A and SMARCA2/BRM losses correlate with reduced CD8 + counts and stage-specific CD4 + infiltration, highlighting their potential as biomarkers for disease progression and immunotherapeutic response.

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PBRM1

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