TGFBR1 KD Mutants in Cancer

Stable Identifier
Homo sapiens
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Mutations in the kinase domain (KD) of TGF-beta receptor 1 (TGFBR1) have been found in Ferguson-Smith tumor i.e. multiple self-healing squamous epithelioma - MSSE (Goudie et al. 2011), breast cancer (Chen et al. 1998), ovarian cancer (Chen et al. 2001) and head-and-neck cancer (Chen et al. 2001). KD mutations reported in MSSE are nonsense and frameshift mutations that cause premature termination of TGFBR1 translation, resulting in truncated receptors that lack substantial portions of the kinase domain, or cause nonsense-mediated decay of mutant transcripts. A splice site KD mutation c.806-2A>C is predicted to result in the skipping of exon 5 and the absence of KD amino acid residues 269-324 from the mutant receptor. The splice site mutant is expressed at the cell surface but unresponsive to TGF-beta stimulation (Goudie et al. 2004).

TGFBR1 KD mutations reported in breast, ovarian and head-and-neck cancer are missense mutations, and it appears that these mutant proteins are partially functional but that their catalytic activity or protein stability is decreased (Chen et al. 1998, Chen et al. 2001a and b). These mutants are not shown.
Literature References
PubMed ID Title Journal Year
11477574 Novel inactivating mutations of transforming growth factor-beta type I receptor gene in head-and-neck cancer metastases

McNiff, J, Leffell, D, Chen, T, Rimm, DL, Wells, RG, Yan, W, Reiss, M

Int. J. Cancer 2001
21358634 Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

Gerdes, AM, Reversade, B, Lee, H, Ferguson-Smith, MA, Whittaker, S, Christie, L, Lane, EB, Nelson, SF, Broesby-Olsen, S, Avery, S, Szeverényi, I, Burrows, N, Stewart, A, Coats, SE, Merriman, B, Hayes, I, Goudie, DR, Friedel, J, D'Alessandro, M, O'Connor, BD, Pichert, G, Lunny, DP, Verma, C

Nat. Genet. 2011
9809982 Transforming growth factor beta type I receptor kinase mutant associated with metastatic breast cancer

Garrigue-Antar, L, Chen, T, Reiss, M, Carter, D

Cancer Res. 1998
11406536 Transforming growth factor-beta receptor type I gene is frequently mutated in ovarian carcinomas

Colligan, B, Chen, T, Graff, JR, Hurst, B, Dehner, B, Pemberton, J, Carter, JH, Triplett, J

Cancer Res. 2001
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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