Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 May 1;80(3-4):489–494. doi: 10.1038/sj.bjc.6690383

Evidence for two candidate tumour suppressor loci on chromosome 9q in transitional cell carcinoma (TCC) of the bladder but no homozygous deletions in bladder tumour cell lines

A A G van Tilborg, L E Groenfeld, T H van der Kwast, E C Zwarthoff
PMCID: PMC2362340  PMID: 10408858

Abstract

The most frequent genetic alterations in transitional cell carcinoma (TCC) of the bladder involve loss of heterozygosity (LOH) on chromosome 9p and 9q. The LOH on chromosome 9p most likely targets the CDKN2 locus, which is inactivated in about 50% of TCCs. Candidate genes that are the target for LOH on chromosome 9q have yet to be identified. To narrow the localization of one or more putative tumour suppressor genes on this chromosome that play a role in TCC of the bladder, we examined 59 tumours with a panel of microsatellite markers along the chromosome. LOH was observed in 26 (44%) tumours. We present evidence for two different loci on the long arm of chromosome 9 where potential tumour suppressor genes are expected. These loci are delineated by interstitial deletions in two bladder tumours. Our results confirm the results of others and contribute to a further reduction of the size of these regions, which we called TCC1 and TCC2. These regions were examined for homozygous deletions with EST and STS markers. No homozygous deletions were observed in 17 different bladder tumour cell lines. © 1999 Cancer Research Campaign

Keywords: bladder cancer, transitional cell carcinoma, chromosome 9, deletion mapping, tumour suppressor genes, loss of heterozygosity

Full Text

The Full Text of this article is available as a PDF (161.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ah-See K. W., Cooke T. G., Pickford I. R., Soutar D., Balmain A. An allelotype of squamous carcinoma of the head and neck using microsatellite markers. Cancer Res. 1994 Apr 1;54(7):1617–1621. [PubMed] [Google Scholar]
  2. Akao T., Kakehi Y., Itoh N., Ozdemir E., Shimizu T., Tachibana A., Sasaki M. S., Yoshida O. A high prevalence of functional inactivation by methylation modification of p16INK4A/CDKN2/MTS1 gene in primary urothelial cancers. Jpn J Cancer Res. 1997 Nov;88(11):1078–1086. doi: 10.1111/j.1349-7006.1997.tb00332.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brewster S. F., Gingell J. C., Browne S., Brown K. W. Loss of heterozygosity on chromosome 18q is associated with muscle-invasive transitional cell carcinoma of the bladder. Br J Cancer. 1994 Oct;70(4):697–700. doi: 10.1038/bjc.1994.376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cairns P., Polascik T. J., Eby Y., Tokino K., Califano J., Merlo A., Mao L., Herath J., Jenkins R., Westra W. Frequency of homozygous deletion at p16/CDKN2 in primary human tumours. Nat Genet. 1995 Oct;11(2):210–212. doi: 10.1038/ng1095-210. [DOI] [PubMed] [Google Scholar]
  5. Cairns P., Shaw M. E., Knowles M. A. Initiation of bladder cancer may involve deletion of a tumour-suppressor gene on chromosome 9. Oncogene. 1993 Apr;8(4):1083–1085. [PubMed] [Google Scholar]
  6. Cairns P., Tokino K., Eby Y., Sidransky D. Localization of tumor suppressor loci on chromosome 9 in primary human renal cell carcinomas. Cancer Res. 1995 Jan 15;55(2):224–227. [PubMed] [Google Scholar]
  7. Chang W. Y., Cairns P., Schoenberg M. P., Polascik T. J., Sidransky D. Novel suppressor loci on chromosome 14q in primary bladder cancer. Cancer Res. 1995 Aug 1;55(15):3246–3249. [PubMed] [Google Scholar]
  8. Corcoran M. M., Rasool O., Liu Y., Iyengar A., Grander D., Ibbotson R. E., Merup M., Wu X., Brodyansky V., Gardiner A. C. Detailed molecular delineation of 13q14.3 loss in B-cell chronic lymphocytic leukemia. Blood. 1998 Feb 15;91(4):1382–1390. [PubMed] [Google Scholar]
  9. Devlin J., Keen A. J., Knowles M. A. Homozygous deletion mapping at 9p21 in bladder carcinoma defines a critical region within 2cM of IFNA. Oncogene. 1994 Sep;9(9):2757–2760. [PubMed] [Google Scholar]
  10. Elder P. A., Bell S. M., Knowles M. A. Deletion of two regions on chromosome 4 in bladder carcinoma: definition of a critical 750kB region at 4p16.3. Oncogene. 1994 Dec;9(12):3433–3436. [PubMed] [Google Scholar]
  11. Habuchi T., Devlin J., Elder P. A., Knowles M. A. Detailed deletion mapping of chromosome 9q in bladder cancer: evidence for two tumour suppressor loci. Oncogene. 1995 Oct 19;11(8):1671–1674. [PubMed] [Google Scholar]
  12. Habuchi T., Luscombe M., Elder P. A., Knowles M. A. Structure and methylation-based silencing of a gene (DBCCR1) within a candidate bladder cancer tumor suppressor region at 9q32-q33. Genomics. 1998 Mar 15;48(3):277–288. doi: 10.1006/geno.1997.5165. [DOI] [PubMed] [Google Scholar]
  13. Habuchi T., Yoshida O., Knowles M. A. A novel candidate tumour suppressor locus at 9q32-33 in bladder cancer: localization of the candidate region within a single 840 kb YAC. Hum Mol Genet. 1997 Jun;6(6):913–919. doi: 10.1093/hmg/6.6.913. [DOI] [PubMed] [Google Scholar]
  14. Jacoby L. B., MacCollin M., Louis D. N., Mohney T., Rubio M. P., Pulaski K., Trofatter J. A., Kley N., Seizinger B., Ramesh V. Exon scanning for mutation of the NF2 gene in schwannomas. Hum Mol Genet. 1994 Mar;3(3):413–419. doi: 10.1093/hmg/3.3.413. [DOI] [PubMed] [Google Scholar]
  15. Keen A. J., Knowles M. A. Definition of two regions of deletion on chromosome 9 in carcinoma of the bladder. Oncogene. 1994 Jul;9(7):2083–2088. [PubMed] [Google Scholar]
  16. Knowles M. A., Shaw M. E., Proctor A. J. Deletion mapping of chromosome 8 in cancers of the urinary bladder using restriction fragment length polymorphisms and microsatellite polymorphisms. Oncogene. 1993 May;8(5):1357–1364. [PubMed] [Google Scholar]
  17. Kohno T., Kawanishi M., Matsuda S., Ichikawa H., Takada M., Ohki M., Yamamoto T., Yokota J. Homozygous deletion and frequent allelic loss of the 21q11.1-q21.1 region including the ANA gene in human lung carcinoma. Genes Chromosomes Cancer. 1998 Mar;21(3):236–243. doi: 10.1002/(sici)1098-2264(199803)21:3<236::aid-gcc8>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  18. Linnenbach A. J., Pressler L. B., Seng B. A., Kimmel B. S., Tomaszewski J. E., Malkowicz S. B. Characterization of chromosome 9 deletions in transitional cell carcinoma by microsatellite assay. Hum Mol Genet. 1993 Sep;2(9):1407–1411. doi: 10.1093/hmg/2.9.1407. [DOI] [PubMed] [Google Scholar]
  19. Merlo A., Gabrielson E., Mabry M., Vollmer R., Baylin S. B., Sidransky D. Homozygous deletion on chromosome 9p and loss of heterozygosity on 9q, 6p, and 6q in primary human small cell lung cancer. Cancer Res. 1994 May 1;54(9):2322–2326. [PubMed] [Google Scholar]
  20. Miura K., Suzuki K., Tokino T., Isomura M., Inazawa J., Matsuno S., Nakamura Y. Detailed deletion mapping in squamous cell carcinomas of the esophagus narrows a region containing a putative tumor suppressor gene to about 200 kilobases on distal chromosome 9q. Cancer Res. 1996 Apr 1;56(7):1629–1634. [PubMed] [Google Scholar]
  21. Nobori T., Miura K., Wu D. J., Lois A., Takabayashi K., Carson D. A. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature. 1994 Apr 21;368(6473):753–756. doi: 10.1038/368753a0. [DOI] [PubMed] [Google Scholar]
  22. Orlow I., Lianes P., Lacombe L., Dalbagni G., Reuter V. E., Cordon-Cardo C. Chromosome 9 allelic losses and microsatellite alterations in human bladder tumors. Cancer Res. 1994 Jun 1;54(11):2848–2851. [PubMed] [Google Scholar]
  23. Polascik T. J., Cairns P., Chang W. Y., Schoenberg M. P., Sidransky D. Distinct regions of allelic loss on chromosome 4 in human primary bladder carcinoma. Cancer Res. 1995 Nov 15;55(22):5396–5399. [PubMed] [Google Scholar]
  24. Ruppert J. M., Tokino K., Sidransky D. Evidence for two bladder cancer suppressor loci on human chromosome 9. Cancer Res. 1993 Nov 1;53(21):5093–5095. [PubMed] [Google Scholar]
  25. Schultz D. C., Vanderveer L., Buetow K. H., Boente M. P., Ozols R. F., Hamilton T. C., Godwin A. K. Characterization of chromosome 9 in human ovarian neoplasia identifies frequent genetic imbalance on 9q and rare alterations involving 9p, including CDKN2. Cancer Res. 1995 May 15;55(10):2150–2157. [PubMed] [Google Scholar]
  26. Shanley S. M., Dawkins H., Wainwright B. J., Wicking C., Heenan P., Eldon M., Searle J., Chenevix-Trench G. Fine deletion mapping on the long arm of chromosome 9 in sporadic and familial basal cell carcinomas. Hum Mol Genet. 1995 Jan;4(1):129–133. doi: 10.1093/hmg/4.1.129. [DOI] [PubMed] [Google Scholar]
  27. Shipman R., Schraml P., Colombi M., Raefle G., Ludwig C. U. Loss of heterozygosity on chromosome 11p13 in primary bladder carcinoma. Hum Genet. 1993 Jun;91(5):455–458. doi: 10.1007/BF00217771. [DOI] [PubMed] [Google Scholar]
  28. Simoneau A. R., Spruck C. H., 3rd, Gonzalez-Zulueta M., Gonzalgo M. L., Chan M. F., Tsai Y. C., Dean M., Steven K., Horn T., Jones P. A. 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 Nov 1;56(21):5039–5043. [PubMed] [Google Scholar]
  29. Southgate J., Proffitt J., Roberts P., Smith B., Selby P. Loss of cyclin-dependent kinase inhibitor genes and chromosome 9 karyotypic abnormalities in human bladder cancer cell lines. Br J Cancer. 1995 Nov;72(5):1214–1218. doi: 10.1038/bjc.1995.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Takle L. A., Knowles M. A. Deletion mapping implicates two tumor suppressor genes on chromosome 8p in the development of bladder cancer. Oncogene. 1996 Mar 7;12(5):1083–1087. [PubMed] [Google Scholar]
  31. Tamimi Y., Bringuier P. P., Smit F., van Bokhoven A., Abbas A., Debruyne F. M., Schalken J. A. Homozygous deletions of p16(INK4) occur frequently in bilharziasis-associated bladder cancer. Int J Cancer. 1996 Oct 9;68(2):183–187. doi: 10.1002/(SICI)1097-0215(19961009)68:2<183::AID-IJC7>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  32. Van Tilborg A. A., Hekman A. C., Vissers K. J., van der Kwast T. H., Zwarthoff E. C. Loss of heterozygosity on chromosome 9 and loss of chromosome 9 copy number are separate events in the pathogenesis of transitional cell carcinoma of the bladder. Int J Cancer. 1998 Jan 5;75(1):9–14. doi: 10.1002/(sici)1097-0215(19980105)75:1<9::aid-ijc2>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  33. Williamson M. P., Elder P. A., Shaw M. E., Devlin J., Knowles M. A. p16 (CDKN2) is a major deletion target at 9p21 in bladder cancer. Hum Mol Genet. 1995 Sep;4(9):1569–1577. doi: 10.1093/hmg/4.9.1569. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES