T-box transcription factor T
T-box transcription factor T, also known as Brachyury protein, is encoded for in humans by the TBXT gene.
Brachyury functions as a transcription factor within the T-box family of genes.
The Brachyury protein is a transcription factor that plays a crucial role in the regulation of gene expression during embryonic development, particularly in the formation of the notochord.
It is also involved in the maintenance of stem cell pluripotency and differentiation.
Mutations in the Brachyury gene have been linked to several developmental disorders, including spina bifida and notochordal tumors.
Chromosome 6
Tissue-culture based techniques have demonstrated one of its roles may be in controlling the velocity of cells as they leave the primitive streak.
It effects transcription of genes required for mesoderm formation and cellular differentiation.
Brachyury has also been shown to help establish the cervical vertebral blueprint during fetal development.
Mutation in this gene has been associated with the development of six or fewer cervical vertebrae instead of the usual seven.
Brachyury is implicated in the initiation and/or progression of a number of tumor types including chordoma, germ cell tumors, hemangioblastoma, GIST, lung cancer, small cell carcinoma of the lung, breast cancer, colon cancer, hepatocellular carcinoma, prostate cancer, and oral squamous carcinoma.
In breast cancer its expression is associated with recurrence, metastasis, reduced survival and resistance to tamoxifen and to cytotoxic chemotherapy.
In lung cancer brachyury expression is associated with recurrence, decreased survival, resistance to cytotoxic chemotherapy, radiation, and EGFR kinase inhibitors.
In prostate cancer brachyury expression is associated with Gleason score, perineural, invasion and capsular invasion.
Brachyury is as a definitive diagnostic marker, key driver and therapeutic target for chordoma, a rare malignant tumor that arises from remnant notochordal cells lodged in the vertebrae.
Brachyury is highly expressed in all chordomas except for the dedifferentiated subtype, which accounts for less than 5% of cases.
Germ line duplication of the brachyury gene is responsible for familial chordoma.
A germline SNP in brachyury is present in 97% of chordoma patients.
Somatic amplifications of brachyury are seen in a subset of sporadic chordomas either by aneuploidy or focal duplication.
Brachyury is the most selectively essential gene in chordoma relative to other cancer types.
Cells that over-express brachyury have down-regulated expression of the adhesion molecule E-cadherin.
Overexpression of brachyury has been linked to hepatocellular carcinoma.
Brachyury expression is a prognostic biomarker for hepatocellular carcinoma.
Overexpression of brachyury may play a part in epithelia mesenchymal transition associated with benign disease such as renal fibrosis.
Brachyury is expressed in tumors but not in normal adult tissues.
Brachyury-specific peptides are presented on HLA receptors of cells in which it is expressed, representing a tumor specific antigen.