Mapping and genome sequence analysis of chromosome 5 regions involved in bladder cancer progression.

 
TitleMapping and genome sequence analysis of chromosome 5 regions involved in bladder cancer progression.
Publication TypeJournal Article
Year of Publication2001
AuthorsKram, A, Li, L, Zhang, RD, Yoon, DS, Ro, JY, Johnston, D, Grossman, HB, Scherer, S, Czerniak, B
JournalLab Invest
Volume81
Issue7
Pagination1039-48
Date Published2001 Jul
ISSN0023-6837
KeywordsAged, Alleles, Chromosome Mapping, Chromosomes, Human, Pair 5, Expressed Sequence Tags, Genome, Humans, Loss of Heterozygosity, Male, Middle Aged, Urinary Bladder Neoplasms
Abstract

We studied the evolution of allelic losses on chromosome 5 by whole-organ histologic and genetic mapping in 234 mucosal DNA samples of 5 cystectomy specimens with invasive bladder cancer and preneoplastic changes in adjacent urothelium. The frequency of alterations in individual loci was verified on 32 tumors and 29 voided urine samples from patients with bladder cancer. Finally, deleted regions on chromosome 5 were integrated with the human genome contigs and sequence-based databases. Deleted regions on chromosome 5 involved in intraurothelial phases of bladder neoplasia defined by their nearest flanking markers and predicted size were identified as follows: q13.3-q22 (D5S424-D5S656; 38.8 centimorgan [cM]); q22-q31.1 (D5S656-D5S808; 19.2 cM), q31.1-q32 (D5S816-SPARC; 11.5 cM), and q34 (GABRA1-D5S415; 6.4 cM). The two most frequently deleted neighbor markers (D5S2055 and D5S818) mapping to q22-q31.1 defined a 9 cM region, which may contain genes that play an important role in early phases of urinary bladder carcinogenesis. Human genome database analysis provided an accurate map of deleted regions with positions of 138 known genes and revealed several smaller gene-rich areas representing putative targets for further mapping. The strategic approach presented here, which combines whole-organ histologic and genetic mapping with analysis of the rapidly emerging human genome sequence database, facilitates identification of genes potentially involved in early phases of bladder carcinogenesis.

Alternate JournalLab. Invest.
PubMed ID11454992
Grant ListR29CA66723 / CA / NCI NIH HHS / United States
UO-1 CA85078 / CA / NCI NIH HHS / United States