CBFB

Overview

CBFB encodes the beta subunit of the core binding factor (CBF) transcription factor complex, which partners with RUNX family proteins to regulate gene expression in hematopoietic and epithelial differentiation. In breast cancer, CBFB is recurrently inactivated by truncating mutations (nonsense and frameshift), particularly in ER-positive tumors. The Broad Institute WES/WGS study of 103 breast tumors was the first to report significant recurrence of CBFB mutations, implicating differentiation transcription factor pathways as a novel axis of breast cancer pathogenesis.

Alterations observed in the corpus

  • CBFB nonsense and frameshift truncating mutations identified in 4% of ER-positive breast cancer samples in WES/WGS of 103 tumors (Broad Institute); first report of significant recurrence in breast cancer PMID:22722202
  • Mutated in breast cancer (TCGA, 510 tumors); CBFB mutations identified as significantly mutated, particularly in luminal A subtype where it acts as a transcription factor complex partner PMID:23000897
  • MYH11-CBFB fusion defines a favorable-risk transcription-factor fusion subgroup in AML; mutually exclusive with NPM1 and DNMT3A mutations PMID:23634996
  • CBFB was identified as a Mut-driver transcription factor in breast cancer (ER+ enriched); inactivating mutations associated with lower tumor grade (OR=0.56), younger age at diagnosis (OR=0.48), and enrichment in IntClust3 (7.8%) and IntClust8 (9.7%); CBFB mutations co-associate with the t(1q;16p) copy-number pattern (OR=5) PMID:27161491.
  • CBFB-MYH11 inv(16)/t(16;16) defines favorable AML subgroup (5%, n=81); HR 0.3 (0.2-0.4) in multivariate survival analysis PMID:27276561
  • CBFB-MYH11 fusion in AML identified as a prognostic marker of low-risk stratification in the PIPseq pediatric precision-oncology cohort (Table 3) PMID:28007021
  • CBFB is a significantly mutated driver in metastatic breast cancer (mBC), also recurrent in early breast cancer (eBC), identified by MutSig analysis of 216 mBC whole-exome sequences vs TCGA primary tumors PMID:28027327
  • Identified in the TCGA pan-cancer fusion landscape as part of the recurrent CBFB-MYH11 fusion in LAML; strongly associated with decreased CBFB (TSG/transcriptional regulator) expression — CBFB is fused but rarely mutated in LAML, representing an alternative inactivation mechanism PMID:29617662.

Cancer types (linked)

  • Breast cancer (BRCA): CBFB truncating mutations enriched in ER-positive (luminal) subtype; inactivation of the CBFB-RUNX1 transcription factor complex implicated in breast tumorigenesis PMID:22722202

Co-occurrence and mutual exclusivity

  • CBFB inactivation co-occurs with RUNX1 homozygous deletion (2 cases) in breast cancer, consistent with functional redundancy in disrupting the CBF transcriptional complex PMID:22722202

Therapeutic relevance

  • CBFB/RUNX1 inactivation highlights differentiation transcription factor pathways as potential therapeutic vulnerabilities in ER-positive breast cancer; functional consequences of CBF complex loss remain to be exploited pharmacologically PMID:22722202

Open questions

  • The precise downstream targets de-regulated by CBFB truncation in breast epithelium, and whether CBFB-mutant tumors have a distinct clinical course or drug response profile, are not yet characterized PMID:22722202

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:23000897

This page was processed by crosslinker on 2026-05-09. - PMID:23634996

This page was processed by crosslinker on 2026-05-09. - PMID:27161491

This page was processed by wiki-cli on 2026-05-14. - PMID:27276561

This page was processed by wiki-cli on 2026-05-14. - PMID:28007021

This page was processed by wiki-cli on 2026-05-14. - PMID:28027327

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

This page was processed by entity-page-writer on 2026-05-15. - PMID:29617662

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