Abstract
Alterations of chromosome 8, including deletions of 8p, occur frequently in many tumors. In this study, fluorescence in situ hybridization was used to study the relationship between 8p deletions, 8q gains, and phenotype in bladder cancer. Cells from 87 tumors were examined by dual-labeling fluorescence in situ hybridization with a centromere 8 probe (pJM12) and P1 probes for 8p22, 8p12, 8q12, and 8q24. Both 8p22 deletions and 8q24 gains were strongly associated with tumor phenotype. There was a marked difference in 8p22 deletions between noninvasive (pTa) tumors (3/33) and minimally invasive (pT1) tumors (8/19; P = 0.005) whereas there was no significant difference between pT1 and muscle-invasive (pT2-4) tumors (19/35; P = 0.3926). Six tumors with 8p22 deletion were examined at 8p12. Three of these tumors showed no 8p12 deletion, narrowing down the site of a putative tumor suppressor gene distal to 8p12. In one other case, there was a marked increase in 8p12 copy number (> 40 per cell; amplification), suggesting the presence of an oncogene involved in bladder cancer at 8p12. The marked difference in 8p22 deletions between noninvasive (pTa) and minimally invasive (pT1) tumors is consistent with a role of a putative tumor suppressor gene on 8p for development of invasive tumor phenotype.
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Selected References
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- Abel P. D., Henderson D., Bennett M. K., Hall R. R., Williams G. Differing interpretations by pathologists of the pT category and grade of transitional cell cancer of the bladder. Br J Urol. 1988 Oct;62(4):339–342. doi: 10.1111/j.1464-410x.1988.tb04361.x. [DOI] [PubMed] [Google Scholar]
- Adnane J., Gaudray P., Dionne C. A., Crumley G., Jaye M., Schlessinger J., Jeanteur P., Birnbaum D., Theillet C. BEK and FLG, two receptors to members of the FGF family, are amplified in subsets of human breast cancers. Oncogene. 1991 Apr;6(4):659–663. [PubMed] [Google Scholar]
- Adélaïde J., Penault-Llorca F., Dib A., Yarden Y., Jacquemier J., Birnbaum D. The Heregulin gene can be included in the 8p12 amplification unit in human breast cancer. Genes Chromosomes Cancer. 1994 Sep;11(1):66–69. doi: 10.1002/gcc.2870110111. [DOI] [PubMed] [Google Scholar]
- Bova G. S., Carter B. S., Bussemakers M. J., Emi M., Fujiwara Y., Kyprianou N., Jacobs S. C., Robinson J. C., Epstein J. I., Walsh P. C. Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer. Cancer Res. 1993 Sep 1;53(17):3869–3873. [PubMed] [Google Scholar]
- Chang M., Tsuchiya K., Batchelor R. H., Rabinovitch P. S., Kulander B. G., Haggitt R. C., Burmer G. C. Deletion mapping of chromosome 8p in colorectal carcinoma and dysplasia arising in ulcerative colitis, prostatic carcinoma, and malignant fibrous histiocytomas. Am J Pathol. 1994 Jan;144(1):1–6. [PMC free article] [PubMed] [Google Scholar]
- Cher M. L., MacGrogan D., Bookstein R., Brown J. A., Jenkins R. B., Jensen R. H. Comparative genomic hybridization, allelic imbalance, and fluorescence in situ hybridization on chromosome 8 in prostate cancer. Genes Chromosomes Cancer. 1994 Nov;11(3):153–162. doi: 10.1002/gcc.2870110304. [DOI] [PubMed] [Google Scholar]
- Cunningham C., Dunlop M. G., Wyllie A. H., Bird C. C. Deletion mapping in colorectal cancer of a putative tumour suppressor gene in 8p22-p21.3. Oncogene. 1993 May;8(5):1391–1396. [PubMed] [Google Scholar]
- Emi M., Fujiwara Y., Ohata H., Tsuda H., Hirohashi S., Koike M., Miyaki M., Monden M., Nakamura Y. Allelic loss at chromosome band 8p21.3-p22 is associated with progression of hepatocellular carcinoma. Genes Chromosomes Cancer. 1993 Jul;7(3):152–157. doi: 10.1002/gcc.2870070307. [DOI] [PubMed] [Google Scholar]
- Fujiwara Y., Emi M., Ohata H., Kato Y., Nakajima T., Mori T., Nakamura Y. Evidence for the presence of two tumor suppressor genes on chromosome 8p for colorectal carcinoma. Cancer Res. 1993 Mar 1;53(5):1172–1174. [PubMed] [Google Scholar]
- Fujiwara Y., Ohata H., Emi M., Okui K., Koyama K., Tsuchiya E., Nakajima T., Monden M., Mori T., Kurimasa A. A 3-Mb physical map of the chromosome region 8p21.3-p22, including a 600-kb region commonly deleted in human hepatocellular carcinoma, colorectal cancer, and non-small cell lung cancer. Genes Chromosomes Cancer. 1994 May;10(1):7–14. doi: 10.1002/gcc.2870100103. [DOI] [PubMed] [Google Scholar]
- Gibas Z., Prout G. R., Pontes J. E., Connolly J. G., Sandberg A. A. A possible specific chromosome change in transitional cell carcinoma of the bladder. Cancer Genet Cytogenet. 1986 Jan 15;19(3-4):229–238. doi: 10.1016/0165-4608(86)90051-8. [DOI] [PubMed] [Google Scholar]
- Hickman D., Risch A., Buckle V., Spurr N. K., Jeremiah S. J., McCarthy A., Sim E. Chromosomal localization of human genes for arylamine N-acetyltransferase. Biochem J. 1994 Feb 1;297(Pt 3):441–445. doi: 10.1042/bj2970441. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jacquemier J., Adelaide J., Parc P., Penault-Llorca F., Planche J., deLapeyriere O., Birnbaum D. Expression of the FGFR1 gene in human breast-carcinoma cells. Int J Cancer. 1994 Nov 1;59(3):373–378. doi: 10.1002/ijc.2910590314. [DOI] [PubMed] [Google Scholar]
- Kallioniemi A., Kallioniemi O. P., Citro G., Sauter G., DeVries S., Kerschmann R., Caroll P., Waldman F. Identification of gains and losses of DNA sequences in primary bladder cancer by comparative genomic hybridization. Genes Chromosomes Cancer. 1995 Mar;12(3):213–219. doi: 10.1002/gcc.2870120309. [DOI] [PubMed] [Google Scholar]
- Knowles M. A., Elder P. A., Williamson M., Cairns J. P., Shaw M. E., Law M. G. Allelotype of human bladder cancer. Cancer Res. 1994 Jan 15;54(2):531–538. [PubMed] [Google Scholar]
- 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]
- Matsumura K., Kallioniemi A., Kallioniemi O., Chen L., Smith H. S., Pinkel D., Gray J., Waldman F. M. Deletion of chromosome 17p loci in breast cancer cells detected by fluorescence in situ hybridization. Cancer Res. 1992 Jun 15;52(12):3474–3477. [PubMed] [Google Scholar]
- Ohata H., Emi M., Fujiwara Y., Higashino K., Nakagawa K., Futagami R., Tsuchiya E., Nakamura Y. Deletion mapping of the short arm of chromosome 8 in non-small cell lung carcinoma. Genes Chromosomes Cancer. 1993 Jun;7(2):85–88. doi: 10.1002/gcc.2870070204. [DOI] [PubMed] [Google Scholar]
- Risch A., Wallace D. M., Bathers S., Sim E. Slow N-acetylation genotype is a susceptibility factor in occupational and smoking related bladder cancer. Hum Mol Genet. 1995 Feb;4(2):231–236. doi: 10.1093/hmg/4.2.231. [DOI] [PubMed] [Google Scholar]
- Sauter G., Carroll P., Moch H., Kallioniemi A., Kerschmann R., Narayan P., Mihatsch M. J., Waldman F. M. c-myc copy number gains in bladder cancer detected by fluorescence in situ hybridization. Am J Pathol. 1995 May;146(5):1131–1139. [PMC free article] [PubMed] [Google Scholar]
- Sauter G., Deng G., Moch H., Kerschmann R., Matsumura K., De Vries S., George T., Fuentes J., Carroll P., Mihatsch M. J. Physical deletion of the p53 gene in bladder cancer. Detection by fluorescence in situ hybridization. Am J Pathol. 1994 Apr;144(4):756–766. [PMC free article] [PubMed] [Google Scholar]
- Sauter G., Moch H., Gasser T. C., Mihatsch M. J., Waldman F. M. Heterogeneity of chromosome 17 and erbB-2 gene copy number in primary and metastatic bladder cancer. Cytometry. 1995 Sep 1;21(1):40–46. doi: 10.1002/cyto.990210109. [DOI] [PubMed] [Google Scholar]
- Sauter G., Moch H., Moore D., Carroll P., Kerschmann R., Chew K., Mihatsch M. J., Gudat F., Waldman F. Heterogeneity of erbB-2 gene amplification in bladder cancer. Cancer Res. 1993 May 15;53(10 Suppl):2199–2203. [PubMed] [Google Scholar]
- Spurr N. K., Blanton S., Bookstein R., Clarke R., Cottingham R., Daiger S., Drayna D., Faber P., Horrigan S., Kas K. Report and abstracts of the second international workshop on human chromosome 8 mapping 1994. Oxford, United Kingdom, September 16-18, 1994. Cytogenet Cell Genet. 1995;68(3-4):147–164. doi: 10.1159/000133908. [DOI] [PubMed] [Google Scholar]
- 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]
- Yaremko M. L., Wasylyshyn M. L., Paulus K. L., Michelassi F., Westbrook C. A. Deletion mapping reveals two regions of chromosome 8 allele loss in colorectal carcinomas. Genes Chromosomes Cancer. 1994 May;10(1):1–6. doi: 10.1002/gcc.2870100102. [DOI] [PubMed] [Google Scholar]
- van der Bosch K., Becker I., Savelyeva L., Brüderlein S., Schlag P., Schwab M. Deletions in the short arm of chromosome 8 are present in up to 90% of human colorectal cancer cell lines. Genes Chromosomes Cancer. 1992 Jul;5(1):91–95. doi: 10.1002/gcc.2870050114. [DOI] [PubMed] [Google Scholar]