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Understanding the development of human bladder cancer by using a whole-organ genomic mapping strategy

Authors
 Tadeusz Majewski  ;  Sangkyou Lee  ;  Joon Jeong  ;  Dong-Sup Yoon  ;  Andrzej Kram  ;  Mi-Sook Kim  ;  Tomasz Tuziak  ;  Jolanta Bondaruk  ;  Sooyong Lee  ;  Weon-Seo Park  ;  Kuang S Tang  ;  Woonbok Chung  ;  Lanlan Shen  ;  Saira S Ahmed  ;  Dennis A Johnston  ;  H Barton Grossman  ;  Colin P Dinney  ;  Jain-Hua Zhou  ;  R Alan Harris  ;  Carrie Snyder  ;  Slawomir Filipek  ;  Steven A Narod  ;  Patrice Watson  ;  Henry T Lynch  ;  Adi Gazdar  ;  Menashe Bar-Eli  ;  Xifeng F Wu  ;  David J McConkey  ;  Keith Baggerly  ;  Jean-Pierre Issa  ;  William F Benedict  ;  Steven E Scherer  ;  Bogdan Czerniak 
Citation
 LABORATORY INVESTIGATION, Vol.88(7) : 694-721, 2008 
Journal Title
 LABORATORY INVESTIGATION 
ISSN
 0023-6837 
Issue Date
2008
MeSH
Aged ; Carcinoma, Transitional Cell/genetics* ; Chromosome Mapping* ; Chromosomes, Human, Pair 13/genetics ; Humans ; Male ; Microsatellite Repeats ; Middle Aged ; Polymorphism, Single Nucleotide ; Retinoblastoma Protein/genetics ; Urinary Bladder/metabolism ; Urinary Bladder/pathology ; Urinary Bladder Neoplasms/genetics* ; Urothelium/metabolism ; Urothelium/pathology
Keywords
forerunner genes ; whole-organ histologic and genetic mapping ; high-resolution mapping with SNPs ; dual-track pathway of bladder cancer development ; apoptosis
Abstract
The search for the genomic sequences involved in human cancers can be greatly facilitated by maps of genomic imbalances identifying the involved chromosomal regions, particularly those that participate in the development of occult preneoplastic conditions that progress to clinically aggressive invasive cancer. The integration of such regions with human genome sequence variation may provide valuable clues about their overall structure and gene content. By extension, such knowledge may help us understand the underlying genetic components involved in the initiation and progression of these cancers. We describe the development of a genome-wide map of human bladder cancer that tracks its progression from in situ precursor conditions to invasive disease. Testing for allelic losses using a genome-wide panel of 787 microsatellite markers was performed on multiple DNA samples, extracted from the entire mucosal surface of the bladder and corresponding to normal urothelium, in situ preneoplastic lesions, and invasive carcinoma. Using this approach, we matched the clonal allelic losses in distinct chromosomal regions to specific phases of bladder neoplasia and produced a detailed genetic map of bladder cancer development. These analyses revealed three major waves of genetic changes associated with growth advantages of successive clones and reflecting a stepwise conversion of normal urothelial cells into cancer cells. The genetic changes map to six regions at 3q22-q24, 5q22-q31, 9q21-q22, 10q26, 13q14, and 17p13, which may represent critical hits driving the development of bladder cancer. Finally, we performed high-resolution mapping using single nucleotide polymorphism markers within one region on chromosome 13q14, containing the model tumor suppressor gene RB1, and defined a minimal deleted region associated with clonal expansion of in situ neoplasia. These analyses provided new insights on the involvement of several non-coding sequences mapping to the region and identified novel target genes, termed forerunner (FR) genes, involved in early phases of cancer development
Files in This Item:
T200806110.pdf Download
DOI
10.1038/labinvest.2008.27
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Dong Sup(윤동섭) ORCID logo https://orcid.org/0000-0001-6444-9606
Jeong, Joon(정준) ORCID logo https://orcid.org/0000-0003-0397-0005
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108623
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