title: FGFR3 mutational status and protein expression in patients with bladder cancer in a Jordanian population.
abstract: Bladder cancer accounts for nearly 5% of all newly diagnosed cancers in Jordan, with a much higher frequency in males. Recent studies have shown that activating mutations in FGFR3 are the most common findings in non-invasive low grade bladder tumors. In this study, we, retrospectively, investigated a cohort of 121 bladder cancer patients with various grades and stages of the tumor for molecular changes in FGFR3. Overexpression of FGFR3 was observed in 49%, 34%, 15%, and 2% of pTa, pT1, pT2, and pT3 cases, respectively. Further, FGFR3 expression was positive in 45%, 26%, and 30% of G1, G2 and G3 cases, respectively. Mutational analysis of exons 7, 10 and 15 of FGFR3 identified four previously reported mutations, namely R248C (n=4; 10%), S249C (n=23; 59%), Y375C (n=7; 18%), G382R (n=4; 10%), and one novel mutation, G382E (n=1; 3%). Our results indicate that both mutations and overexpression of FGFR3 are correlated together, and are more prevalent in early stage (pTa and pT1) and low grade (G1 and G2) bladder tumors. Survival analysis showed no contribution of changes in FGFR3 on the patient's survival. Multivariate Cox proportional hazards model analysis of overall survival for the following variables: age, gender, stage and grade of tumor, and FGFR3 (expression and mutation) revealed that age, stage and grade of tumor are independent predictors of overall survival in patients with bladder cancer. Our work is the first to address the molecular status of FGFR3 in Jordanian patients with bladder cancer, and provides further support for FGFR3 as a key player in the initiation of bladder tumors.
authors.affiliation: Department of Applied Biology, Jordan University of Science and Technology, Irbid, Jordan. khaldon.bodoor@duke.edu
authors.forename: Khaldon
authors.initials: K
authors.lastname: Bodoor
authors.forename: Abdulhameed
authors.initials: A
authors.lastname: Ghabkari
authors.forename: Ziad
authors.initials: Z
authors.lastname: Jaradat
authors.forename: Asem
authors.initials: A
authors.lastname: Alkhateeb
authors.forename: Saied
authors.initials: S
authors.lastname: Jaradat
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Al-Ghazo
authors.forename: Ismail
authors.initials: I
authors.lastname: Matalka
authors.forename: Hisham
authors.initials: H
authors.lastname: Musleh
authors.forename: Yazan
authors.initials: Y
authors.lastname: Haddad
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007597:Jordan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3