Abstracts
Résumé
Le cancer de la vessie se présente sous deux formes différentes: la forme superficielle et la forme infiltrante. La forme superficielle se caractérise par une fréquence élevée de pertes (totales ou partielles) du chromosome 9, notamment du bras long. Ces observations suggèrent la présence de gènes suppresseurs de tumeur (GST) dans cette région. Nous présentons le gène PATCHED, localisé en position 9q22.3, déjà impliqué dans le carcinome basocellulaire de la peau, comme un GST potentiel dans le cancer superficiel de la vessie.
Summary
Superficial bladder cancer shows a high frequency of total or partial chromosome 9 losses. Loss of heterozygosity at position 9q22.3 is one of the most frequent and is associated with highly recurrent tumours. The PATCHED gene, ortholog of a gene first described in the drosophila as a segment polarity gene, is located at 9q22.3. It is a member of a signal transduction pathway and a tumour suppressor gene (TSG), involved in basal cell carcinoma. We propose PATCHED as a TSG candidate in superficial bladder cancer.
Appendices
Références
- 1. Knowles MA. The genetics of transitional cell carcinoma: progress and potential clinical application. BJU Int 1999; 84: 412-27.
- 2. Simoneau M, Aboulkassim TO, Larue H, Rousseau F, Fradet Y. Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two novel candidate regions at 9q22.3 and 9q31. Oncogene 1999; 18: 157-63.
- 3. 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 1999; 18: 1185-96.
- 4. Williams SV, Sibley KD, Davies AM, et al. Molecular genetic analysis of chromosome 9 candidate tumor-suppressor loci in bladder cancer cell lines. Genes Chrom Cancer 2002; 34: 86-96.
- 5. Bartlett JMS, Watters AD, Ballantyne SA, Going JJ, Grigor KM, Cooke TG. Is chromosome 9 loss a marker of disease recurrence in transitional cell carcinoma of the urinary bladder? Br J Cancer 1998; 77: 2193-8.
- 6. Simoneau M, Larue H, Aboulkassim TO, Meyer F, Moore L, Fradet Y. Chromosome 9 deletions and recurrence of superficial bladder cancer: identification of four regions of prognostic interest. Oncogene 2000; 19: 6317-23.
- 7. Aboulkassim TO, Larue H, Lemieux P, Rousseau F, Fradet Y. Alteration of the Patched locus in superficial bladder cancer. Oncogene 2003; 22: 2967-71.
- 8. Wicking C, Smyth I, Bale A. The hedgehog signalling pathway in tumorigenesis and development. Oncogene 1999; 18: 7844-51.
- 9. Bale AE, Yu KP. The hedgehog pathway and basal cell carcinomas. Hum Mol Genet 2001; 10: 757-62.
- 10. Goodrich LV, Johnson RL, Milenkovic L, McMahon JA, Scott MP. Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog. Genes Dev 1996; 10: 301-12.
- 11. Villavicencio EH, Walterhouse DO, Iannaccone PM. The sonic hedgehog-patched-gli pathway in human development and disease. Am J Hum Genet 2000; 67: 1047-54.
- 12. Altaba A. Gli proteins encode context-dependent positive and negative functions: implications for development and disease. Development 1999; 126: 3205-16.
- 13. Duman-Scheel M, Weng L, Xin S, Du W. Hedgehog regulates cell growth and proliferation by inducing cyclin D and cyclin E. Nature 2002; 417: 299-304.
- 14. Yoon JW, Kita Y, Frank DJ, et al. Gene expression profiling leads to identification of GLI1-binding elements in target genes and a role for multiple downstream pathways in GLI1-induced cell transformation. J Biol Chem 2002; 277: 5548-55.
- 15. McGarvey TW, Maruta Y, Tomaszewski JE, Linnenbach AJ, Malkowicz SB. PTCH gene mutations in invasive transitional cell carcinoma of the bladder. Oncogene 1998; 17: 1167-72.
- 16. Simoneau AR, Spruck CH 3rd, Gonzalez-Zulueta M, et al. Evidence for two tumor suppressor loci associated with proximal chromosome 9p to q and distal chromosome 9q in bladder cancer and the initial screening for GAS1 and PTC mutations. Cancer Res 1996; 56: 5039-43.
- 17. Xie J, Johnson RL, Zhang X, et al. Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors. Cancer Res 1997; 57: 2369-72.
- 18. Ohgaki K, Minobe K, Kurose K, et al. Two target regions of allelic loss on chromosome 9 in urinary-bladder cancer. Jpn J Cancer Res 1999; 90: 957-64.
- 19. Velickovic M, Delahunt B, McIver B, Grebe SK. Intragenic PTEN/MMAC1 loss of heterozygosity in conventional (clear-cell) renal cell carcinoma is associated with poor patient prognosis. Mod Pathol 2002; 15: 479-85.
- 20. Xu X, Brodie SG, Yang X, et al. Haploid loss of the tumor suppressor Smad4/Dpc4 initiates gastric polyposis and cancer in mice. Oncogene 2000; 19: 1868-74.
- 21. Philipp-Staheli J, Payne SR, Kemp CJ. p27(Kip1): regulation and function of a haploinsufficient tumor suppressor and its misregulation in cancer. Exp Cell Res 2001; 264: 148-68.
- 22. Zurawel RH, Allen C, Wechsler-Reya R, Scott MP, Raffel C. Evidence that haploinsufficiency of Ptch leads to medulloblastoma in mice. Genes Chrom Cancer 2000; 28: 77-81.