|Variant(s)||FBXW7 codon(s) 505, 465 missense|
FBXW7 is a tumor suppressor gene responsible for the degradation of several proto-oncogenes. mTOR is one of the substrates of FBXW7-mediated protein degradation, and loss of function of FBXW7 increases the levels of total and activated mTOR. Codons 465 and 505 are some of the most frequently mutated sites in the FBXW7 gene. FBXW7 is mutated in approximately 15% of small bowel cancers. Preclinical data have suggested that inactivating mutations of FBXW7 could predict sensitivity to the mTOR inhibitor rapamycin; however, the clinical utility remains unknown.
Jardim DL, Wheler JJ, Hess K, et al. FBXW7 Mutations in Patients with Advanced Cancers: Clinical and Molecular Characteristics and Outcomes with mTOR Inhibitors. Li JJ, ed. PLoS ONE. 2014;9(2):e89388. doi:10.1371/journal.pone.0089388.
Mao JH, Kim IJ, Wu D, Climent J, Kang HC, et al. (2008) FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression. Science 321: 1499--1502.
Zehir A, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017 Jun;23(6):703-713.
Disclaimer: You assume full responsibility for all risks associated with using this PMKB website. The IPM makes no guarantee of the comprehensiveness, reliability or accuracy of the information on this website and the IPM assumes no responsibility for errors in the information associated with this web site. Healthcare providers and patients must integrate all clinical and laboratory findings as well as information from a variety of sources before deciding on appropriate clinical care options.