TBX3

Overview

TBX3 encodes a T-box transcription factor that regulates stem cell pluripotency and developmental patterning. In cancer, TBX3 mutations have been implicated as a novel cancer driver in breast cancer. Notably, common inherited variants at the TBX3 locus confer small increased risks of breast cancer, linking germline predisposition to somatic driver mutations at the same locus. Recurrent in-frame deletions in TBX3 observed in breast tumors suggest a functionally constrained domain important for its tumor suppressive activity.

Alterations observed in the corpus

  • Mutations in 6 of 100 breast tumors in WES (Sanger cohort); recurrent in-frame deletions at Thr210 and Asn212 suggest a functionally important domain; TBX3 identified as a newly discovered cancer driver gene PMID:22722201
  • Common inherited variants at TBX3 locus confer small increased breast cancer risk, linking germline predisposition to somatic driver function PMID:22722201
  • Identified as a significantly mutated gene in TCGA breast cancer cohort (510 tumors); TBX3 encodes a T-box transcription factor recurrently mutated in breast cancer PMID:23000897
  • ILC-enriched mutations (9% ILC vs 2% IDC) in TCGA/METABRIC integrated analysis of invasive lobular carcinoma PMID:26451490
  • Transcription-factor Mut-driver in breast cancer; co-mutated with CDH1 (characteristic of lobular carcinoma biology, OR not specified) in the 2,433-tumour METABRIC targeted-sequencing cohort PMID:27161491.
  • A-allele-preferring binder at rs4519489 identified by PWAS proteomics and EEL motif analysis, but no ChIP-qPCR enrichment at the locus — not a confirmed regulator in this study PMID:28927585
  • Identified as a novel recurrently mutated gene in metastatic colorectal cancer (mCRC). PMID:29316426

Cancer types (linked)

  • Breast cancer (BRCA): Novel cancer driver gene; recurrent mutations in 6% of tumors with functionally significant in-frame deletions at Thr210/Asn212 PMID:22722201

Co-occurrence and mutual exclusivity

  • No specific co-mutation patterns reported in the corpus for TBX3.

Therapeutic relevance

  • No direct targeted therapies described in the corpus for TBX3-mutant tumors. TBX3 role in stem cell pluripotency programs may offer indirect therapeutic angles.

Open questions

  • The precise mechanism by which TBX3 in-frame deletions at Thr210/Asn212 drive breast cancer (loss-of-function vs. dominant-negative) is not established in the corpus.
  • Frequency and significance of TBX3 mutations across breast cancer subtypes (ER+, HER2+, TNBC) requires larger cohort validation.

Sources

  • PMID:22722201 — Breast cancer WES, 100 tumors, Sanger Institute

This page was processed by crosslinker on 2026-05-14. - PMID:23000897

This page was processed by crosslinker on 2026-05-14. - PMID:26451490

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

This page was processed by wiki-cli on 2026-05-14. - PMID:28927585

This page was processed by wiki-cli on 2026-05-15. - PMID:29316426

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