TY - JOUR
T1 - Mapping and genome sequence analysis of chromosome 5 regions involved in bladder cancer progression
AU - Kram, Andrzej
AU - Li, Li
AU - Zhang, Ruo Dan
AU - Yoon, Dong Sup
AU - Ro, Jae
AU - Johnston, Dennis
AU - Grossman, Herbert Barton
AU - Scherer, Steven
AU - Czerniak, Bogdan
N1 - Funding Information:
This work was supported by National Institutes of Health Grants R29CA66723 and UO-1 CA85078 to BC. Address reprint requests to: Dr. Bogdan Czerniak, University of Texas, M.D. Anderson Cancer Center, Department of Pathology, Box 085, 1515 Holcombe Boulevard, Houston, Texas 77030-4009. E-mail: bczernia@ mdanderson.org
PY - 2001
Y1 - 2001
N2 - 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 eady phases of bladder carcinogenesis.
AB - 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 eady phases of bladder carcinogenesis.
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U2 - 10.1038/labinvest.3780315
DO - 10.1038/labinvest.3780315
M3 - Article
C2 - 11454992
AN - SCOPUS:0034932776
SN - 0023-6837
VL - 81
SP - 1039
EP - 1048
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 7
ER -