Loss of heterozygosity on chromosome 9q and p53 alterations in human bladder cancer.
BACKGROUND
Somatic loss of the 9q allele as well as alteration of the tumor suppressor p53 occurs commonly in bladder cancers. Although alteration of p53 has been strongly associated with invasive stage disease, the prognostic significance of 9q loss of heterozygosity (LOH) and the relations between these alterations are less well defined.


METHODS
The 9q LOH was examined at five microsatellites and p53 alterations (mutation and persistent immunohistochemical staining) in a population-based case series of 271 newly diagnosed bladder cancer patients. Loss of heterozygosity was scored quantitatively and p53 mutation completed using single-strand conformation polymorphism screening followed by sequencing.


RESULTS
Overall, allelic loss at 9q was detected in 74.5% (202/271) of cases and allele loss was associated with invasive disease (P < 0.05). Although based on small numbers, all nine in situ lesions contained 9q LOH. Age, gender, and smoking were not significantly associated with chromosome 9q allele loss. Both intense persistent p53 staining and LOH at 9q were independently associated with invasive disease (P < 10(-14) and P < 0.05, respectively).


CONCLUSIONS
These data, using a population-based sample, suggest a relation between 9q LOH and invasive stage bladder cancer, and thereby suggests that a tumor suppressor gene at this loci, in addition to p53, may be important in the development of this more aggressive form of the disease.
Hirao
Shuya
S
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Hirao
Tomoko
T
Marsit
Carmen J
CJ
Hirao
Yoko
Y
Schned
Alan
A
Devi-Ashok
Tara
T
Nelson
Heather H
HH
Andrew
Angeline
A
Karagas
Margaret R
MR
Kelsey
Karl T
KT
D000328:Adult; D000368:Aged; D002899:Chromosomes, Human, Pair 9; D018450:Disease Progression; D005260:Female; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000235:genetics*