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

Tomasz Tuziak, Joon Jeong, 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

21 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

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'High-resolution whole-organ mapping with SNPs and its significance to early events of carcinogenesis'. Together they form a unique fingerprint.

  • Cite this

    Tuziak, T., Jeong, J., Majewski, T., Kim, M. S., Steinberg, J., Wang, Z., Yoon, D. S., Kuang, T. C., Baggerly, K., Johnston, D., & Czerniak, B. (2005). High-resolution whole-organ mapping with SNPs and its significance to early events of carcinogenesis. Laboratory Investigation, 85(5), 689-701. https://doi.org/10.1038/labinvest.3700270