Clinical and biological characteristics of cervical neoplasias with FGFR3 mutation.
BACKGROUND
We have previously reported activating mutations of the gene coding for the fibroblast growth factor receptor 3 (FGFR3) in invasive cervical carcinoma. To further analyze the role of FGFR3 in cervical tumor progression, we extended our study to screen a total of 75 invasive tumors and 80 cervical intraepithelial neoplasias (40 low-grade and 40 high-grade lesions).


RESULTS
Using single strand conformation polymorphism (SSCP) followed by DNA sequencing, we found FGFR3 mutation (S249C in all cases) in 5% of invasive cervical carcinomas and no mutation in intraepithelial lesions. These results suggest that, unlike in bladder carcinoma, FGFR3 mutation does not or rarely occur in non invasive lesions. Compared to patients with wildtype FGFR3 tumor, patients with S249C FGFR3 mutated tumors were older (mean age 64 vs. 49.4 years, P = 0.02), and were more likely to be associated with a non-16/18 HPV type in their tumor. Gene expression analysis demonstrated that FGFR3 mutated tumors were associated with higher FGFR3b mRNA expression levels compared to wildtype FGFR3 tumors. Supervised analysis of Affymetrix expression data identified a significant number of genes specifically differentially expressed in tumors with respect to FGFR3 mutation status.


CONCLUSIONS
This study suggest that tumors with FGFR3 mutation appear to have distinctive clinical and biological characteristics that may help in defining a population of patients for FGFR3 mutation screening.
Rosty
Christophe
C
Département de Pathologie, Institut Curie, Section Médicale, 26 rue d'Ulm, 75248 Paris Cedex 05, France. christophe.rosty@curie.fr
Aubriot
Marie-Hélène
MH
Cappellen
David
D
Bourdin
Jérôme
J
Cartier
Isabelle
I
Thiery
Jean Paul
JP
Sastre-Garau
Xavier
X
Radvanyi
François
F
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018307:Neoplasms, Squamous Cell / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D012694:Serine / Q000235:genetics; D015996:Survival Rate; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology*
D012333:RNA, Messenger; D012694:Serine; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3