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Superimposed histologic and genetic mapping of chromosome 9 in progression of human urinary bladder neoplasia: implications for a genetic model of multistep urothelial carcinogenesis and early detection of urinary bladder cancer

Oncogene volume 18, pages 1185–1196 (1999)Cite this article

Abstract

The evolution of alterations on chromosome 9, including the putative tumor suppressor genes mapped to the 9p21-22 region (the MTS genes), was studied in relation to the progression of human urinary bladder neoplasia by using whole organ superimposed histologic and genetic mapping in cystectomy specimens and was verified in urinary bladder tumors of various pathogenetic subsets with long-term follow-up. The applicability of chromosome 9 allelic losses as non-invasive markers of urothelial neoplasia was tested on voided urine and/or bladder washings of patients with urinary bladder cancer. Although sequential multiple hits in the MTS locus were documented in the development of intraurothelial precursor lesions, the MTS genes do not seem to represent a major target for p21-23 deletions in bladder cancer. Two additional tumor suppressor genes involved in bladder neoplasia located distally and proximally to the MTS locus within p22-23 and p11-13 regions respectively were identified. Several distinct putative tumor suppressor gene loci within the q12-13, q21-22, and q34 regions were identified on the q arm. In particular, the pericentromeric q12-13 area may contain the critical tumor suppressor gene or genes for the development of early urothelial neoplasia. Allelic losses of chromosome 9 were associated with expansion of the abnormal urothelial clone which frequently involved large areas of urinary bladder mucosa. These losses could be found in a high proportion of urothelial tumors and in voided urine or bladder washing samples of nearly all patients with urinary bladder carcinoma.

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Acknowledgements

We would like to thank Donna Sprabary for secretarial assistance. This work was supported in part by NIH grants CA66723-04 to Bogdan Czerniak and CA54672 and EYO6195 to William F Benedict.

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Authors and Affiliations

  1. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Bogdan Czerniak, Vijaya Chaturvedi, Li Li, Sherie Hodges, Jae Y Ro, Rajyalakshmi Luthra & John G Batsakis

  2. Department of Biomathematics, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Dennis Johnston

  3. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Christopher Logothetis & William F Benedict

  4. Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Andrew C Von Eschenbach & H Barton Grossman

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  1. Bogdan Czerniak
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Czerniak, B., Chaturvedi, V., Li, L. et al. Superimposed histologic and genetic mapping of chromosome 9 in progression of human urinary bladder neoplasia: implications for a genetic model of multistep urothelial carcinogenesis and early detection of urinary bladder cancer. Oncogene 18, 1185–1196 (1999). https://doi.org/10.1038/sj.onc.1202385

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