High-resolution whole-organ mapping with SNPs and its significance to early events of carcinogenesis

Tomasz Tuziak, Jeong Joon, Tadeusz Majewski, Mi Sook Kim, Jordan Steinberg, Zhi Wang, Dong Sup Yoon, Tang C. Kuang, Keith Baggerly, Dennis Johnston, Bogdan Czerniak

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We attempted to identify deleted segments in two model tumor suppressor gene loci on chromosomes 13q14 and 17p13 that were associated with clonal expansion of in situ bladder preneoplasia using single nucleotide polymorphisms (SNPs)-based whole-organ histologic and genetic mapping. For mapping with SNPs, the sequence-based maps spanning approximately 27 and 5 Mb centered around RB1 and p53, respectively, were assembled. The integrated gene and SNP maps of the regions were used to select 661 and 960 SNPs, which were genotyped by pyrosequencing. Genotyping of SNPs was performed on DNA samples corresponding to histologic maps of the entire bladder mucosa in human cystectomy specimens with invasive urothelial carcinoma. By using this approach, we have identified deleted regions associated with clonal expansion of intraurothelial neoplasia; which ranged from 0.001 to 4.3 Mb (average 0.67 Mb) and formed clusters of discontinuous deleted segments. The high resolution of such maps is a prerequisite for future positional targeting of genes involved in early phases of bladder neoplasia. This approach also permits analysis of the overall genomic landscape of the involved region and discloses that a unique composition of noncoding DNA characterized by a high concentration of repetitive sequences may predispose to deletions.

Original languageEnglish
Pages (from-to)689-701
Number of pages13
JournalLaboratory Investigation
Volume85
Issue number5
DOIs
Publication statusPublished - 2005 May 1

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Single Nucleotide Polymorphism
Carcinogenesis
Urinary Bladder
Gene Targeting
Nucleic Acid Repetitive Sequences
Cystectomy
DNA
Tumor Suppressor Genes
Neoplasms
Mucous Membrane
Chromosomes
Carcinoma
Genes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Tuziak, Tomasz ; Joon, Jeong ; Majewski, Tadeusz ; Kim, Mi Sook ; Steinberg, Jordan ; Wang, Zhi ; Yoon, Dong Sup ; Kuang, Tang C. ; Baggerly, Keith ; Johnston, Dennis ; Czerniak, Bogdan. / High-resolution whole-organ mapping with SNPs and its significance to early events of carcinogenesis. In: Laboratory Investigation. 2005 ; Vol. 85, No. 5. pp. 689-701.
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Tuziak, T, Joon, J, Majewski, T, Kim, MS, Steinberg, J, Wang, Z, Yoon, DS, Kuang, TC, Baggerly, K, Johnston, D & Czerniak, B 2005, 'High-resolution whole-organ mapping with SNPs and its significance to early events of carcinogenesis', Laboratory Investigation, vol. 85, no. 5, pp. 689-701. https://doi.org/10.1038/labinvest.3700270

High-resolution whole-organ mapping with SNPs and its significance to early events of carcinogenesis. / Tuziak, Tomasz; Joon, Jeong; Majewski, Tadeusz; Kim, Mi Sook; Steinberg, Jordan; Wang, Zhi; Yoon, Dong Sup; Kuang, Tang C.; Baggerly, Keith; Johnston, Dennis; Czerniak, Bogdan.

In: Laboratory Investigation, Vol. 85, No. 5, 01.05.2005, p. 689-701.

Research output: Contribution to journalArticle

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