Loss of Function of TGFBR1 in Cancer

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R-HSA-3656534
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Homo sapiens
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TGF-beta receptor 1 (TGFBR1) loss-of-function is a less frequent mechanism for inactivation of TGF-beta signaling in cancer compared to SMAD4 and TGFBR2 inactivation. Genomic deletion of TGFBR1 locus has been reported in pancreatic cancer (Goggins et al. 1998), biliary duct cancer (Goggins et al. 1998) and lymphoma (Schiemann et al. 1999), while loss-of-function mutations have been reported in breast (Chen et al. 1998) and ovarian cancer (Chen et al. 2001), metastatic head-and-neck cancer (Chen et al. 2001), and in Ferguson-Smith tumors (multiple self-healing squamous epithelioma - MSSE) (Goudie et al. 2011). Loss-of-function mutations mainly affect the ligand-binding extracellular domain of TGFBR1 and the kinase domain of TGFBR1 (Goudie et al. 2011). In the mouse model of colorectal cancer, Tgfbr1 haploinsufficiency cooperates with Apc haploinsufficiency in the development of intestinal tumors (Zeng et al. 2009).

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
9850059 Genetic alterations of the transforming growth factor beta receptor genes in pancreatic and biliary adenocarcinomas

Yeo, CJ, Kern, SE, Hruban, RH, Goggins, M, Shekher, M, Turnacioglu, K

Cancer Res. 1998
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
10515889 A deletion in the gene for transforming growth factor beta type I receptor abolishes growth regulation by transforming growth factor beta in a cutaneous T-cell lymphoma

Lodish, HF, Levi, E, Schiemann, WP, Kadin, ME, Pfeifer, WM

Blood 1999
19147584 Tgfbr1 haploinsufficiency is a potent modifier of colorectal cancer development

Phukan, S, Zeng, Q, Pasche, B, Yang, GY, Liao, J, Xu, Y, Rosman, DS, Valle, L, de la Chapelle, A, Huang, CC, Pennison, M, Di Cristofano, A, Sadim, M

Cancer Res. 2009
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
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Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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