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.

  • Oncogenomics
  • Published:

Alteration of the PATCHED locus in superficial bladder cancer

Abstract

Chromosome 9 alterations are the most frequently encountered cytologic anomalies in urothelial carcinoma (UC). We previously screened 139 low-stage UCs for loss of heterozygosity on chromosome 9, and identified five distinct regions likely to harbour tumour-suppressor genes. The present study focused on deletion mapping in the 9q22 region with 11 additional microsatellite markers. New deletions in the 9q22 region were found in five tumours. Deletion mapping allowed us to identify a 0.5 CM common minimal region of deletion between markers D9S280 and D9S1809, encompassing PATCHED (PTC), a gene identified as a tumour suppressor in basal cell carcinoma and in medulloblastoma. A marker located in the first intron of this gene showed the highest percentage of deletion (45%). cDNA sequencing in 15 tumours with deletion of PTC showed no mutation in the remaining allele. However, average expression of PTC mRNA measured by semiquantitative RT–PCR was significantly decreased in tumours with LOH in the 9q22 region, compared to normal urothelium (P=0.04), while it showed marked fluctuations in tumours without deletion. Our results suggest that the PTC gene is a putative suppressor at the 9q22 locus and that haploinsufficiency of this gene may be an early event in the development of papillary bladder tumours.

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

Access options

Buy this article

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

  • Bale AE and Yu KP . (2001). Hum. Mol. Genet., 10, 757–762.

  • Cairns P, Shaw ME and Knowles MA . (1993). Cancer Res., 53, 1230–1232.

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

  • Calzada-Wack J, Kappler R, Schnitzbauer U, Richter T, Nathrath M, Rosemann M, Wagner SN, Hein R and Hahn H . (2002). Carcinogenesis, 23, 727–733.

  • Chen Y and Struhl G . (1996). Cell, 87, 553–563.

  • Czerniak B, Chaturvedi V, Li L, Hodges S, Johnston D, Ro JY, Luthra R, Logothetis C, Von Eschenbach AC, Grossman HB, Benedict WF and Batsakis JG . (1999). Oncogene, 18, 1185–1196.

  • Fero ML, Randel E, Gurley KE, Roberts JM and Kemp CJ . (1998). Nature, 396, 177–180.

  • Gailani MR, Stahle-Backdahl M, Leffell DJ, Glynn M, Zaphiropoulos PG, Pressman C, Unden AB, Dean M, Brash DE, Bale AE and Toftgard R . (1996). Nat. Genet., 14, 78–81.

  • Gibson RA, Buchwald M, Roberts RG and Mathew CG . (1993). Hum. Mol. Genet., 2, 35–38.

  • Goodrich LV, Johnson RL, Milenkovic L, McMahon JA and Scott MP . (1996). Genes Dev., 10, 301–312.

  • Gorlin RJ . (1987). Medicine (Baltimore), 66, 98–113.

  • Habuchi T, Luscombe M, Elder PA and Knowles MA . (1998). Genomics, 48, 277–288.

  • Hahn H, Wicking C, Zaphiropoulos PG, Gailani MR, Schanley S, Chidambaram A, Vorechoysky I, Holmberg E, Unden AN, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B and Bale AE . (1996). Cell, 85, 841–851.

  • Hornigold N, Devlin J, Davies AM, Aveyard JS, Habuchi T and Knowles MA . (1999). Oncogene, 18, 2657–2661.

  • Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein Jr EH and Scott MP . (1996). Science, 272, 1668–1671.

  • Kallassy M, Toftgard R, Ueda M, Nakazawa K, Vorechovsky I, Yamasaki H and Nakazawa H . (1997). Cancer Res., 57, 4731–4735.

  • Knudson AG . (1993). Proc. Natl. Acad. Sci. USA, 90, 10914–10921.

  • Kupfer GM, Yamashita T, Naf D, Suliman A, Asano S and D'Andrea AD . (1997). Blood, 90, 1047–1054.

  • Marigo V, Davey RA, Zuo Y, Cunningham JM and Tabin CJ . (1996). Nature, 384, 176–179.

  • Maurice D, Pierreux CE, Howell M, Wilentz RE, Owen MJ and Hill CS . (2001). J. Biol. Chem., 276, 43175–43181.

  • Oro AE, Higgins KM, Hu Z, Bonifas JM, Epstein Jr EH and Scott MP . (1997). Science, 276, 817–821.

  • Philipp-Staheli J, Payne SR and Kemp CJ . (2001). Exp. Cell Res., 264, 148–168.

  • Simoneau M, Aboulkassim TO, Larue H, Rousseau F and Fradet Y . (1999). Oncogene, 18, 157–163.

  • Simoneau M, Larue H, Aboulkassim TO, Meyer F, Moore L and Fradet Y . (2000). Oncogene, 19, 6317–6323.

  • Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, Scott MP, Pennica D, Goddard A, Phillips H, Noll M, Hooper JE, de Sauvage F and Rosenthal A . (1996). Nature, 384, 129–134.

  • Tanaka M, Mullauer L, Ogiso Y, Fujita H, Moriya S, Furuuchi K, Harabayashi T, Shinohara N, Koyanagi T and Kuzumaki N . (1995). Cancer Res., 55, 3228–3232.

  • Vanni R, Scarpa RM, Nieddu M and Usai E . (1988). Cancer Genet. Cytogenet., 30, 35–42.

  • Velickovic M, Delahunt B, McIver B and Grebe SK . (2002). Mod. Pathol., 15, 479–485.

  • Wicking C, Smyth I and Bale A . (1999). Oncogene, 18, 7844–7851.

  • Wu Q, Possati L, Montesi M, Gualandi F, Rimessi P, Morelli C, Trabanelli C and Barbanti-Brodano G . (1996). Int. J. Cancer, 65, 840–846.

  • Xie J, Johnson RL, Zhang X, Bare JW, Waldman FM, Cogen PH, Menon AG, Warren RS, Chen LC, Scott MP and Epstein Jr EH . (1997). Cancer Res., 57, 2369–2372.

  • Xu X, Brodie SG, Yang X, Im YH, Parks WT, Chen L, Zhou YX, Weinstein M, Kim SJ and Deng CX . (2000). Oncogene, 19, 1868–1874.

  • Yamashita T, Barber DL, Zhu Y, Wu N and D'Andrea AD . (1994). Proc. Natl. Acad. Sci. USA, 91, 6712–6716.

  • Zhang L, Cui X, Schmitt K, Hubert R, Navidi W and Arnheim N . (1992). Proc. Natl. Acad. Sci. USA, 89, 5847–5851.

  • Zurawel RH, Allen C, Wechsler-Reya R, Scott MP and Raffel C . (2000). Genes Chromosomes Cancer, 28, 77–81.

Download references

Acknowledgements

This work was supported by the National Cancer Institute of Canada grant # 011347 with funds from the Canadian Cancer Society. FR is a senior scientist of the Fonds de la Recherche en Santé du Québec.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yves Fradet.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aboulkassim, T., LaRue, H., Lemieux, P. et al. Alteration of the PATCHED locus in superficial bladder cancer. Oncogene 22, 2967–2971 (2003). https://doi.org/10.1038/sj.onc.1206513

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206513

Keywords

This article is cited by

Search

Quick links