TY - JOUR
T1 - Role of activating fibroblast growth factor receptor 3 mutations in the development of bladder tumors
AU - Zieger, Karsten
AU - Dyrskjøt, Lars
AU - Wiuf, Carsten
AU - Jensen, Jens L.
AU - Andersen, Claus L.
AU - Jensen, Klaus Møller Ernst
AU - Ørntoft, Torben Falck
PY - 2005/11/1
Y1 - 2005/11/1
N2 - Purpose: Bladder tumors develop through different molecular pathways. Recent reports suggest activating mutations of the fibroblast growth factor receptor 3 (FGFR3) gene as marker for the "papillary" pathway with good prognosis, in contrast to the more malignant "carcinoma in situ" (CIS) pathway. The aim of this clinical follow-up study was to investigate the role of FGFR3 mutations in bladder cancer development in a longitudinal study. Experimental Design: We selected 85 patients with superficial bladder tumors, stratified into early (stage Ta/grade 1-2, n = 35) and more advanced (either stage T1 or grade 3, n = 50) developmental stages. The patients were followed prospectively, and metachronous tumors were included. We did screening for FGFR3 and TP53 mutations by direct bidirectional sequencing and for genome-wide molecular changes with microarray technology. Results: A total of 43 of 85 cases (51%) showed activating mutations of FGFR3. The mutations were associated with papillary tumors of early developmental stage. However, after stratifying for developmental stage, FGFR3-mutated tumors showed the same malignant potential as wild-type tumors. Tumors with concomitant CIS were generally FGFR3 wild type. They were characterized by different patterns of chromosomal changes and gene expression signatures compared with FGFR3-mutated tumors, indicating different molecular pathways. Conclusions: FGFR3 mutations seem to have a central role in the early development of papillary bladder tumors. These tumors follow a common molecular pathway, which is different from tumors with concomitant CIS. FGFR3 mutations do not seem to play a role in bladder cancer progression.
AB - Purpose: Bladder tumors develop through different molecular pathways. Recent reports suggest activating mutations of the fibroblast growth factor receptor 3 (FGFR3) gene as marker for the "papillary" pathway with good prognosis, in contrast to the more malignant "carcinoma in situ" (CIS) pathway. The aim of this clinical follow-up study was to investigate the role of FGFR3 mutations in bladder cancer development in a longitudinal study. Experimental Design: We selected 85 patients with superficial bladder tumors, stratified into early (stage Ta/grade 1-2, n = 35) and more advanced (either stage T1 or grade 3, n = 50) developmental stages. The patients were followed prospectively, and metachronous tumors were included. We did screening for FGFR3 and TP53 mutations by direct bidirectional sequencing and for genome-wide molecular changes with microarray technology. Results: A total of 43 of 85 cases (51%) showed activating mutations of FGFR3. The mutations were associated with papillary tumors of early developmental stage. However, after stratifying for developmental stage, FGFR3-mutated tumors showed the same malignant potential as wild-type tumors. Tumors with concomitant CIS were generally FGFR3 wild type. They were characterized by different patterns of chromosomal changes and gene expression signatures compared with FGFR3-mutated tumors, indicating different molecular pathways. Conclusions: FGFR3 mutations seem to have a central role in the early development of papillary bladder tumors. These tumors follow a common molecular pathway, which is different from tumors with concomitant CIS. FGFR3 mutations do not seem to play a role in bladder cancer progression.
UR - http://www.scopus.com/inward/record.url?scp=27744515561&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-05-1130
DO - 10.1158/1078-0432.CCR-05-1130
M3 - Journal article
C2 - 16278391
AN - SCOPUS:27744515561
SN - 1078-0432
VL - 11
SP - 7709
EP - 7719
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 21
ER -
