Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Genetic mapping and DNA sequence-based analysis of deleted regions on chromosome 16 involved in progression of bladder cancer from occult preneoplastic conditions to invasive disease

Abstract

Histologic and genetic mapping with 30 hypervariable markers mapped to chromosome 16 were performed on 234 DNA samples of five cystectomy specimens from patients with invasive bladder cancer. Allelic losses of individual markers were related to microscopically identified precursor conditions in the entire bladder mucosa and invasive cancer. Their significance for the development and progression of neoplasia from in situ preneoplastic conditions to invasive disease was analysed by the nearest neighbor algorithm and binomial maximum likelihood analysis. Using this approach we identified five distinct regions of allelic losses defined by their flanking markers and predicted size as follows. p13.3(D16S418-D16S406, 1.2 cM), p13.1(D16S748-D16S287, 12.9 cM), q12 1(D16S409-D16S514, 24.0 cM), q22.1 (D16S496-D16S515, 5.4 cM), and q24 (D16S507-D16S511, 5.9 cM and D16S402-D16S413, 17.4 cM). The regions mapping to p13.1 and q24 were involved in early intraurothelial phases of bladder neoplasia such as mild to moderate dysplasia. On the other hand the deleted region mapping to p13.3 was involved in progression of severe dysplasia/carcinoma in situ to invasive bladder cancer. Testing of markers that exhibited statistically significant LOH in relation to progression of neoplasia from precursor conditions to invasive cancer on 28 tumors and voided urine samples from 25 patients with bladder cancer revealed that q12.1 showed LOH in 46.4% of tumor and 32.0% of voided urine samples. The LOH of a single marker D16S541 could be detected in approximately 28% of tumors and 20% of voided urine samples of patients with bladder cancer. These data imply that the deleted region centered around marker D16S541 spanning approximately 10 cM and flanked by D16S409 and D16S415 contains a novel putative tumor suppressor gene or genes playing an important role in the development of human bladder cancer. To facilitate more precise positional mapping and identification of pathogenetically relevent genes, we analysed of human genome contig and sequence databases spanning the deleted regions. Multiple known candidate genes and several smaller gene-rich areas mapping to the target regions of chromosome 16 were identified.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Asgeirsson KS, Jonasson JG, Tryggvad L, Olafsd K, Sigurgeirsd JR, Ingvarsson S, Ogmundsd HM . 2000 Eur. J. Cancer 36: 1098–1106

  • Brownlee KA . 1965 Statistical Theory and Methodology in Science and Engineering 2nd edn John Wiley & Sons, Inc. New York

    Google Scholar 

  • Cairns P, Tokino K, Eby Y, Sidransky D . 1994 Cancer Res. 54: 1422–1424

  • Carter BS, Ewing CM, Ward WS, Treiger BF, Aalders TW, Schalken JA, Epstein JI, Isaacs WB . 1990 Proc. Natl. Acad. Sci. USA 87: 8751–8755

  • Chang WYH, Cairns P, Schoenberg MP, Polascik TJ, Sidransky D . 1995 Cancer Res. 55: 3246–3249

  • Chaturvedi V, Li L, Hodges S, Johnston D, Ro JY, Logothetis C, Eschenbach A, Batsakis J, Czerniak B . 1997 Oncogene 14: 2059–2070

  • Czerniak B, Chaturvedi V, Li L, Hodges S, Johnston D, Ro JY, Luthra R, Logothetis C, Eschen bach A, Grossman B, Benedict WF, Batsakis JG . 1999 Oncogene 18: 1185–1196

  • Czerniak B Cohen GL, Etkind P, Deitch D, Simmons H, Herz F, Koss LG . 1992 Hum. Pathol. 23: 1199–1204

  • Czerniak B, Li L, Chaturvedi V, Ro JY, Johnston D, Hodges S, Benedict WF . 2000 Genes. Chromosomes. Cancer 27: 392–402

  • Czerniak B, Herz F . 1995 Diagnostic Cytology of the Urinary Tract with Histopathologic and Clinical Correlations Koss LG (ed) Lippincott-Raven: Philadelphia pp 345–359

    Google Scholar 

  • Devilee P, Van Vliet M, Van Sloun P, Kuipers-Dijkshoorn N, Hermans J, Pearson PL, Cornelisse CJ . 1991 Oncogene 6: 1705–1711

  • Dutrillaux B, Gerbault-Seureau M, Zafrani B . 1990 Cancer Genet. Cytogenet. 49: 203–217

  • Gyapay G, Morissette J, Vignal A, Dib C, Fizames C, Millasseau P, Marc S, Bernardi G, Lathrop M, Weissenbach J . 1994 Nat. Genet. 7: 246–339

  • Hartigan JA . 1975 Clustering Algorithms John Wiley & Sons, Inc. New York

    Google Scholar 

  • Hughes TR, Roberts CJ, Dai H, Jones AR, Meyer MR, Slade D, Burchard J, Dow S, Ward TR, Kidd MJ, Friend SH, Marton MJ . 2000 Nat. Genet. 25: 333–337

  • Koss LG . 1979 Hum. Pathol. 10: 533–548

  • Koss LG, Czerniak B . 1991 N. Engl. J. Med. 324: 125–126

  • Koss LG, Nakanishi I, Freed SZ . 1977 Urology 9: 442–455

  • Koss LG, Tiamson EM, Robbins MA . 1974 JAMA 227: 281–286

  • Larsson C, Byrstrom C, Skoog L, Rotstein S, Nordenskjold M . 1990 Genes. Chromosome Cancer 2: 191–197

  • Lininger RA, Park WS, Man YG, Pham T, Macgrogan G, Zhuang Z, Tavassoli FA . 1998 Human Pathol. 29: 1113–1118

  • Lucito R, West J, reiner A, Alexander J, Esposito D, Mishra B, Powers S, Norton L, Wigler M . 2000 Genome Res. 10: 1726–1736

  • Mao L, Schoenberg MP, Scicchitano M, Erozan YS, Merlo A, Schwab D, Sidransky D . 1996 Science 271: 659–662

  • Mostofi FK (ed.) . 1999 Histological Typing of Urinary Bladder Tumors Springer: New York

    Book  Google Scholar 

  • Ott J . 1991 Analysis of Human Genetic Linkage Johns Hopkins University Press: Baltimore

    Google Scholar 

  • Pan Y, Matsuyama H, Wang N, Yoshihiro S, Haggarth L, Li C, Tribukait B, Ekman P, Bergerheim US . 1998 Prostate 36: 31–38

  • Rodgers CS, Hill SM, Hulten M . 1984 Cancer Genet. Cytogenet. 13: 95–119

  • Sato T, Tanigami A, Yamakawa K, Akiyama F, Kasumi F, Saka OG, Nakamura Y . 1990 Cancer Res. 50: 7184–7189

  • Sato M, Mori Y, Sakurada A, Fukushige S, Ishikawa Y, Tsuchiya E, Saito Y, Nukiwa T, Fujimura S, Hori A . 1998 Genes Chromosomes Cancer 22: 1–8

  • Sobin LH, Wittekind C . 1997 TNM classification of malignant tumors 5th ed Wiley-Liss, New York

    Google Scholar 

  • Spruck CH III, Ohneseit PF, Gonzalez-Zulueta M, Esrig D, Noriomi M, Tsai YC, Lerner SP, Schumutte Yang AS, Cote R, Dubeau LD, Nichols PW, Hermann GG, Steven K, Horn T, Skinner DG, Jones PA . 1994 Cancer Res. 54: 784–788

  • Steiner G, Schoenberg MP, Linn JF, Mao L, Sidransky D . 1997 Nature Med. 3: 621–624

  • Tsuda H, Zhang W, Shimosato Y, Yokota J, Terada M, Sugimura T, Miyamura T, Hirohashi S . 1990 Proc. Natl. Acad. Sci. USA 87: 6791–6794

  • Whitmore SA, Crawford J, Apostolou S, Eyre H, Baker E, Lower KM, Settasatian C, Goldup S, Seshadri R, Gibson RA, Mathew CG, Cleton-Jansen AM, Savoia A, Pronk JC, Auerbach AD, Doggett NA, Sutherland GR, Callen DF . 1998 Genomics 50: 1–8

Download references

Acknowledgements

This work was supported by National Institutes of Health grants R29CA66723 and UO-1 CA85078 to Bogdan Czerniak.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bogdan Czerniak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoon, DS., Li, L., Zhang, RD. et al. Genetic mapping and DNA sequence-based analysis of deleted regions on chromosome 16 involved in progression of bladder cancer from occult preneoplastic conditions to invasive disease. Oncogene 20, 5005–5014 (2001). https://doi.org/10.1038/sj.onc.1204612

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204612

Keywords

This article is cited by

Search

Quick links