PMID- 11971182
OWN - NLM
STAT- MEDLINE
DCOM- 20020508
LR  - 20161124
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 21
IP  - 16
DP  - 2002 Apr 11
TI  - Amplification pattern of 12q13-q15 genes (MDM2, CDK4, GLI) in urinary bladder 
      cancer.
PG  - 2476-83
AB  - The chromosomal region 12q13-q15 is recurrently amplified in bladder cancer. 
      Putative target genes located in this region include MDM2, CDK4, and GLI. To 
      evaluate the involvement of these genes in bladder cancer, we screened a tissue 
      microarray (TMA) containing 2317 samples by fluorescence in situ hybridization 
      (FISH). Amplification was found for MDM2 in 5.1%, for CDK4 in 1.1%, and for GLI 
      in 0.4% of interpretable tumors. Among tumors having amplification of at least 
      one of these 12q13-q15 genes, 76.6% had amplification of MDM2 alone and 6.4% had 
      amplification of CDK4 alone. Coamplifications were seen of MDM2 and CDK4 in 
      10.6%, and of CDK4 and GLI in 6.4%. Neither coamplifications of all three genes 
      nor isolated GLI amplifications were found. These data suggest a prominent role 
      of MDM2 as a 12q13-q15 amplification target in bladder cancer. However, 
      independent CDK4 amplifications do also occur suggesting either two 
      non-overlapping amplification sites or else a minimal overlapping region between 
      MDM2 and CDK4 perhaps containing another yet unknown oncogene. The frequency of 
      amplification increased significantly from stage pTa to pT1-4 (P<0.04) and from 
      low to high grade (P<0.005). These data are consistent with a high level of 
      genetic instability in invasively growing and high-grade bladder tumors.
FAU - Simon, Ronald
AU  - Simon R
AD  - Institute for Pathology and Urologic Clinics, University of Basel, 
      Schoenbeinstrasse 40, CH-4003 Basel, Switzerland.
FAU - Struckmann, Kirsten
AU  - Struckmann K
FAU - Schraml, Peter
AU  - Schraml P
FAU - Wagner, Urs
AU  - Wagner U
FAU - Forster, Thomas
AU  - Forster T
FAU - Moch, Holger
AU  - Moch H
FAU - Fijan, Andre
AU  - Fijan A
FAU - Bruderer, James
AU  - Bruderer J
FAU - Wilber, Kim
AU  - Wilber K
FAU - Mihatsch, Michael J
AU  - Mihatsch MJ
FAU - Gasser, Thomas
AU  - Gasser T
FAU - Sauter, Guido
AU  - Sauter G
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Chromosomes, Human, Pair 12
MH  - Cyclin-Dependent Kinase 4
MH  - Cyclin-Dependent Kinases/*genetics/metabolism
MH  - *Gene Amplification
MH  - Humans
MH  - *Nuclear Proteins
MH  - Oligonucleotide Array Sequence Analysis
MH  - Oncogene Proteins/*genetics/metabolism
MH  - Prognosis
MH  - Proto-Oncogene Proteins/*genetics/metabolism
MH  - Proto-Oncogene Proteins c-mdm2
MH  - RNA, Neoplasm/biosynthesis
MH  - Survival Analysis
MH  - Trans-Activators
MH  - Transcription Factors/*genetics/metabolism
MH  - Urinary Bladder Neoplasms/*genetics/metabolism/mortality
MH  - Zinc Finger Protein GLI1
EDAT- 2002/04/24 10:00
MHDA- 2002/05/09 10:01
CRDT- 2002/04/24 10:00
PHST- 2001/06/18 00:00 [received]
PHST- 2002/01/02 00:00 [revised]
PHST- 2002/01/08 00:00 [accepted]
PHST- 2002/04/24 10:00 [pubmed]
PHST- 2002/05/09 10:01 [medline]
PHST- 2002/04/24 10:00 [entrez]
AID - 10.1038/sj.onc.1205304 [doi]
PST - ppublish
SO  - Oncogene. 2002 Apr 11;21(16):2476-83. doi: 10.1038/sj.onc.1205304.