NCOR1

Overview

NCOR1 (Nuclear Receptor Corepressor 1) encodes a transcriptional corepressor that interacts with nuclear receptors, including the estrogen receptor (ER), to suppress target gene transcription. Homozygous deletions of NCOR1 in breast cancer were identified in the METABRIC CNA-expression analysis, nominating it as a novel candidate driver. NCOR1 loss may de-repress ER-driven transcriptional programs, with implications for hormone receptor-positive breast cancer biology.

Alterations observed in the corpus

  • NCOR1 homozygous deletions identified as rare but potentially significant events in the METABRIC breast cancer cohort (~2,000 tumors) by integrated CNA-expression analysis PMID:22522925
  • NCOR1 nominated as a novel candidate driver gene alongside MDM4 and CDK4 by expression outlier analysis PMID:22522925
  • Truncating mutations and homozygous deletions identified in breast cancer WES (100 tumors, Sanger cohort); participates in oestrogen receptor alpha transcriptional repression PMID:22722201
  • Chromatin-remodeling gene mutated as part of the cohesin/chromatin-modifier landscape in TCC bladder cancer; mutations totaling 58% of 99 UCGC cases across chromatin-remodeling genes PMID:24121792
  • In mCRPC, NCOR1 was identified as an AR pathway regulator recurrently altered in the 150-patient SU2C–PCF prospective cohort. PMID:26000489
  • AR co-activator alteration enriched in CRPC-Adeno (21 cases) vs. CRPC-NE PMID:26855148
  • NCOR1 identified as a mutation-driver in breast cancer in a 2,433-tumor whole-genome/exome sequencing study (METABRIC/ICGC cohort) PMID:27161491
  • Among the most frequently mutated epigenetic modifiers in the DUX4/ERG B-ALL subtype; epigenetic-modifier mutations overall present in 56.3% of cases PMID:27776115
  • NCOR1 was identified as a functional tumor suppressor in DLBCL by CRISPR screen (its knockout was enriched, indicating growth suppression function); alterations in NCOR1 were associated with poorer prognosis specifically in GCB DLBCL PMID:28985567

Cancer types (linked)

  • BRCA (Breast cancer): Homozygous deletions detected in METABRIC cohort; expression outlier analysis confirms cis-acting loss PMID:22522925

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • NCOR1 loss may de-repress estrogen receptor target genes; the relationship to endocrine therapy sensitivity in ER-positive breast cancer is not addressed in the current corpus.

Open questions

  • Functional validation of NCOR1 as a tumor suppressor in breast cancer is needed; its role in specific IntClust subtypes defined by METABRIC remains to be characterized.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22722201

This page was processed by crosslinker on 2026-05-14. - PMID:24121792

This page was processed by crosslinker on 2026-05-14. - PMID:26000489

This page was processed by crosslinker on 2026-05-14. - PMID:26855148

This page was processed by wiki-cli on 2026-05-14. - PMID:27161491

This page was processed by wiki-cli on 2026-05-14. - PMID:27776115

This page was processed by entity-page-writer on 2026-05-15. - PMID:28985567

This page was processed by wiki-cli on 2026-05-15.