PBRM1

Overview

PBRM1 (Polybromo-1) encodes a chromatin-remodeling subunit of the SWI/SNF complex. Loss-of-function mutations in PBRM1 are commonly observed in renal cell carcinoma and have been reported across gynecologic cancers. PBRM1 has been investigated as a potential biomarker for immunotherapy response, given the role of SWI/SNF in regulating immune recognition pathways.

Alterations observed in the corpus

  • PBRM1 and ARID2 (SWI/SNF complex members) were mutated in dMMR/MSI-H gynecologic cancers treated with nivolumab; no significant difference in mutation rates was observed between responders and non-responders PMID:38653864.
  • Loss-of-function mutations in PBRM1 define a molecular subtype of ccRCC associated with distinct immune infiltration and immunotherapy response patterns PMID:22138691
  • Mutated as part of SWI/SNF and broader chromatin-remodeling alterations present in 24% of esophageal adenocarcinomas (EAC), alongside ARID1A, ARID2, SMARCA4, and JARID2 PMID:23525077
  • Significantly mutated gene (SMG) in clear cell renal cell carcinoma (q<0.00001); SWI/SNF (PBAF) subunit enriched in m1 mRNA subtype (39% vs 27%); co-occurs in HotNet PBAF subnetwork with ARID1A and SMARCA4 PMID:23792563
  • SWI/SNF complex subunit mutated in 8/64 (13%) intrahepatic cholangiocarcinomas (IHCH) and 4/16 (25%) gallbladder carcinomas (GBC); previously known mainly from clear-cell renal cell carcinoma; mutation may confer sensitivity to chromatin-remodeling-targeted therapies such as HDAC inhibitors PMID:24185509
  • Flagged as a SWI/SNF chromatin-remodeling complex partner (alongside ARID1B) in the genomic landscape of sinonasal adenoid cystic carcinoma PMID:24418857
  • PBRM1 is mutated in 6/10 ccRCC tumors; truncal in 3 of those 6. Two distinct PBRM1 frameshifts (p.Lys1282fs and p.Leu207fs) coexisted in RMH004 (parallel evolution), illustrating intratumor heterogeneity of this SWI/SNF subunit PMID:24487277
  • PBRM1 (BAF180), a PBAF-specific SWI/SNF subunit, is referenced in the context of complex composition in small cell carcinoma of the ovary, hypercalcemic type (SCCOHT); not mutated in this cohort but relevant to SWI/SNF biology PMID:24658004
  • Recurrent loss-of-function mutations in thymic carcinomas, part of a molecular profile that distinguishes aggressive thymic carcinomas from indolent thymomas PMID:24974848
  • Invoked as precedent for discovering frequent kidney-cancer driver mutations from modest sample sizes (originally identified in ccRCC from 25 tumors); not somatically recurrent in the ChRCC cohort (n=66) PMID:25155756
  • In pancreatic ductal adenocarcinoma (PAAD), PBRM1 was altered in 5% of cases as part of the SWI/SNF chromatin-remodelling complex lesions affecting >42% of cases in the 109-case microdissected exome cohort. PMID:25855536
  • Added to significant gene list by inactivation-bias test in a periampullary cancer WGS study (DUOAC/AMPAC/CAC); alteration type not individually specified for PBRM1 in this cohort PMID:26804919
  • PBRM1 (SWI/SNF subunit) mutated as part of a chromatin-remodelling complex enriched in ATC vs PDTC (SWI/SNF subunit mutations in 36% ATC vs 6% PDTC, P=1×10⁻⁴); mutations generally mutually exclusive within the complex. PMID:26878173
  • Identified as a Mut-driver gene (inactivating mutations) in the METABRIC 2,433-tumor breast cancer cohort; classified as a SWI/SNF chromatin-function driver (22.6% of all tumors had a coding mutation in ≥1 of seven chromatin-function Mut-drivers including PBRM1). Raises possibility of synthetic-lethal vulnerabilities analogous to ARID1A/ARID1B in the breast cancer setting. PMID:27161491
  • Mutated in 3% of unclassified RCC (uRCC) cases in a 62-sample MSK-IMPACT cohort; co-occurs with other chromatin-remodeling gene mutations distinguishing uRCC from ccRCC (VHL-low) PMID:27713405
  • SWI/SNF complex member; more frequently altered in esophageal adenocarcinoma (EAC) than esophageal squamous cell carcinoma (ESCC) in a multi-platform genomic study of gastroesophageal adenocarcinoma PMID:28052061
  • S275 mutation in 1/19 (5%) of 1p/19q-codeleted anaplastic oligodendroglioma PMID:28472509
  • Biallelic LOF (truncating mutation + chr3p loss) enriched in anti-PD-(L)1 responders in ccRCC; PBRM1-LOF tumors show up-regulated hypoxia and JAK/STAT3 programs and reduced immune-inhibitory ligand expression PMID:29301960
  • Called as a KIRC SMG by both MutSig2CV and MuSiC2 in the MC3 pan-cancer open-access MAF covering 10,510 TCGA tumor/normal pairs across 33 cancer types PMID:29596782.

Cancer types (linked)

  • Endometrial cancer (UCEC) / ovarian cancer (OVT) — PBRM1 mutations detected in the dMMR/MSI-H gynecologic cancer cohort; not differentially enriched by response to PD-1 blockade PMID:38653864.

Co-occurrence and mutual exclusivity

  • Co-occurs with other SWI/SNF complex alterations (ARID1A 82%, ARID2) in the dMMR gynecologic cancer cohort PMID:38653864.

Therapeutic relevance

  • PBRM1 mutations are not predictive of nivolumab response in dMMR/MSI-H gynecologic cancers; they were present in both responders and non-responders at similar rates PMID:38653864.

Open questions

  • Whether PBRM1 loss acts as a modifier of immunotherapy response in specific gynecologic cancer subtypes (e.g., PBRM1-mutant vs. wild-type endometrial cancer) requires further study.

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:29301960

This page was processed by entity-page-writer on 2026-05-15. - PMID:29596782

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