title: Oncogenic Activation of Fibroblast Growth Factor Receptor-3 and RAS Genes as Non-Overlapping Mutual Exclusive Events in Urinary Bladder Cancer.
abstract: BACKGROUND
  Urinary bladder cancer is a common malignancy in the West and ranks as the 7th most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases.
  
  
  METHODS
  Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing.
  
  
  RESULTS
  Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3.
  
  
  CONCLUSIONS
  We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.
authors.affiliation: Advanced Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India E-mail : arshaajizskims@gmail.com.
authors.forename: Arshad A
authors.initials: AA
authors.lastname: Pandith
authors.forename: Aashaq
authors.initials: A
authors.lastname: Hussain
authors.forename: Mosin S
authors.initials: MS
authors.lastname: Khan
authors.forename: Zafar A
authors.initials: ZA
authors.lastname: Shah
authors.forename: M Saleem
authors.initials: MS
authors.lastname: Wani
authors.forename: Mushtaq A
authors.initials: MA
authors.lastname: Siddiqi
mesh_terms: D014408:Biomarkers, Tumor; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D008565:Membrane Proteins; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)