Loss of Function of TGFBR2 in Cancer

Stable Identifier
Homo sapiens
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Loss-of-function of transforming growth factor-beta receptor II (TGFBR2) is most prevalent in colorectal cancer. Over 60% of colorectal cancers with microsatellite instability (MSI) harbor inactivating mutations in both alleles of TGFBR2, mostly 1 or 2 bp deletions in the 10 bp adenine repeat that codes for three lysine residues in the extracellular domain of TGFBR2. These small deletions result in a frameshift and a premature stop codon (Markowitz et al. 1995). TGFBR2 kinase domain (KD) mutations are found in ~20% of microsatellite stable (MSS) colorectal cancers and these are mostly missense mutations that results in substitution of conserved amino acids in the kinase domain (Grady et al. 1999), likely impairing the catalytic activity of TGFBR2 KD mutants. The silencing of TGFBR2 gene via promoter methylation has been reported in B-cell lymphoma (Chen et al. 2007). Knockout of murine Tgfbr2 in colonic epithelium promotes azoxymethane-induced colon cancer formation (Biswas et al. 2004) and increases the number of adenomas and adenocarcinomas in Apc+/- mice (Munoz et al. 2006).
Literature References
PubMed ID Title Journal Year
17047044 Transforming growth factor beta receptor type II inactivation induces the malignant transformation of intestinal neoplasms initiated by Apc mutation

Muñoz, NM, Madison, BB, Washington, MK, Moses, HL, Pozzi, A, Chytil, A, Rojas, A, Moon, RT, Upton, M, Lin, L, Sozmen, EG, Grady, WM

Cancer Res. 2006
7761852 Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability

Fan, RS, Sun, L, Vogelstein, B, Myeroff, L, Wang, J, Kinzler, KW, Parsons, R, Markowitz, S, Zborowska, E, Lutterbaugh, J

Science 1995
15256431 Transforming growth factor beta receptor type II inactivation promotes the establishment and progression of colon cancer

Romero-Gallo, J, Wirth, PS, Moses, HL, Washington, K, Chytil, A, Biswas, S, Gorska, AE, Gautam, S, Grady, WM

Cancer Res. 2004
17339425 Resistance to TGF-beta 1 correlates with aberrant expression of TGF-beta receptor II in human B-cell lymphoma cell lines

Ghosh, P, Rezanka, L, O'Farrell, TJ, Chen, G, Sasaki, CY, Osawa, H, Yang, J, Longo, DL

Blood 2007
9927040 Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers

Kinzler, KW, Willson, JK, Grady, WM, Chang, J, Vogelstein, B, Swinler, SE, Kim, SJ, Myeroff, L, Neumann, A, Brattain, MG, Lutterbaugh, JD, Rajput, A, Markowitz, S, Thiagalingam, S

Cancer Res. 1999
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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