Chromosome 9 deletions are more frequent than FGFR3 mutations in flat urothelial hyperplasias of the bladder.
Flat urothelial hyperplasias (FUHs) in patients with papillary bladder tumours frequently show deletions of chromosome 9, suggesting that FUH could be the first neoplastic step in the development of papillary bladder cancer. FGFR3 mutations are frequent in non-invasive papillary tumours with low risk of progression. Our aim was to investigate the frequency of FGFR3 mutations and deletions of chromosomes 9p/q and 8p/q in FUH. Thirty FUH and 9 simultaneous or consecutive tumours were detected by 5-ALA-based photodynamic cystoscopy. DNA was isolated from frozen sections and whole genome amplification was done by I-PEP-PCR, followed by LOH analysis on chromosomes 8p/q and 9p/q. FGFR3 mutations were detected by SNaPshot analysis. LOH analysis on FUH revealed deletions at 9p/q (11/30, 37%) and 8p/q (3/30, 10%). FGFR3 mutations were found in 7/30 FUH (23%). Only 2 FUH showed an FGFR3 mutation without deletions of chromosome 9. In contrast, 6 FUH revealed chromosome 9 deletions but wild type FGFR3 (p = 0.03). These results suggest that chromosome 9 deletions are the earliest genetic alterations in bladder cancer. The detection of FGFR3 mutations in FUH further supports the role of this lesion as precursor of papillary bladder cancer.
Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, the Netherlands.
Johanna M M
JM
van Oers
Christoph
C
Adam
Stefan
S
Denzinger
Robert
R
Stoehr
Simone
S
Bertz
Dirk
D
Zaak
Christian
C
Stief
Ferdinand
F
Hofstaedter
Ellen C
EC
Zwarthoff
Theodorus H
TH
van der Kwast
Ruth
R
Knuechel
Arndt
A
Hartmann
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8; D002899:Chromosomes, Human, Pair 9; D005260:Female; D017353:Gene Deletion; D006801:Humans; D006965:Hyperplasia / Q000235:genetics; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D001743:Urinary Bladder / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3