PMID- 10830781
OWN - NLM
STAT- MEDLINE
DCOM- 20000608
LR  - 20230216
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 80
IP  - 5
DP  - 2000 May
TI  - Clonality and genetic divergence in multifocal low-grade superficial urothelial 
      carcinoma as determined by chromosome 9 and p53 deletion analysis.
PG  - 709-18
AB  - Multifocality and recurrence are clinically important features of urothelial 
      carcinomas of the urinary bladder. Recent molecular genetic studies have 
      suggested that multifocal urothelial carcinomas are monoclonally derived from an 
      identical transformed progenitor cell. However, most of these studies 
      investigated advanced and poorly differentiated tumors. The study presented 
      focuses on early papillary tumors, including 52 superficial well-differentiated 
      multifocal and recurrent bladder carcinomas from 10 patients. Microdissection 
      separating urothelium from stromal cells was considered essential to obtain pure 
      tumor cell populations. Genetic analysis was carried out by applying two 
      different methods. Dual color fluorescence in situ hybridization (FISH) with 
      centromeric probes for chromosomes 9 and 17 and gene-specific probes for 
      chromosome loci 9q22, 9p21, and 17p13 was carried out in parallel to loss of 
      heterozygosity (LOH) analyses applying 5 microsatellite markers on these 
      chromosomes. Overall, deletions on chromosome 9p were found in 47 tumors (90%), 
      at chromosome 9q in 36 tumors (69%) and at chromosome 17p in 3 tumors (6%). There 
      was a very high correlation of the results between FISH and LOH analysis. Ten 
      early superficial papillary tumors showed deletion of chromosome 9p without 
      deletion of 9q, suggesting 9p deletions as a very early event in the development 
      of papillary urothelial carcinoma. Although in four patients, all investigated 
      tumors showed identical genetic alterations and one patient showed no genetic 
      alterations at the loci investigated, in five patients, two or more clones with 
      different deletions were found. In four of these patients, the results are 
      compatible with clonal divergence and selection of different cell subpopulations 
      derived from a common progenitor cell. However, in one patient different alleles 
      in two markers at chromosome 9 were deleted, favoring an independent evolution of 
      two recurring tumor cell clones. In summary, we could show that there is 
      considerable genetic heterogeneity in early multifocal and recurring urothelial 
      carcinoma and demonstrated the occurrence of two independent clones in at least 
      one patient as an indicator of possible initial oligoclonality of bladder cancer.
FAU - Hartmann, A
AU  - Hartmann A
AD  - Institute of Pathology, University of Regensburg, Germany.
FAU - Rosner, U
AU  - Rosner U
FAU - Schlake, G
AU  - Schlake G
FAU - Dietmaier, W
AU  - Dietmaier W
FAU - Zaak, D
AU  - Zaak D
FAU - Hofstaedter, F
AU  - Hofstaedter F
FAU - Knuechel, R
AU  - Knuechel R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
SB  - IM
MH  - Aged
MH  - *Chromosomes, Human, Pair 9
MH  - *Genes, p53
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Loss of Heterozygosity
MH  - Male
MH  - Microsatellite Repeats
MH  - Middle Aged
MH  - Urinary Bladder Neoplasms/*genetics/pathology
EDAT- 2000/06/01 09:00
MHDA- 2000/06/10 09:00
CRDT- 2000/06/01 09:00
PHST- 2000/06/01 09:00 [pubmed]
PHST- 2000/06/10 09:00 [medline]
PHST- 2000/06/01 09:00 [entrez]
AID - S0023-6837(22)02171-7 [pii]
AID - 10.1038/labinvest.3780074 [doi]
PST - ppublish
SO  - Lab Invest. 2000 May;80(5):709-18. doi: 10.1038/labinvest.3780074.