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. 1993 Sep 1;90(17):8038–8042. doi: 10.1073/pnas.90.17.8038

Susceptibility to renal carcinoma in the Eker rat involves a tumor suppressor gene on chromosome 10.

R S Yeung 1, K H Buetow 1, J R Testa 1, A G Knudson Jr 1
PMCID: PMC47283  PMID: 8103600

Abstract

Germ-line mutations of tumor suppressor genes confer strong predisposition to tumor formation. In the rat, a form of dominantly inherited renal carcinoma (RC) results in multiple chromophobe cell tumors that resemble the human disease, and heterozygous carriers (RC/+) are highly susceptible to environmental agents (radiation and chemical carcinogens), making it a desirable model to study epithelial carcinogenesis. By linkage analysis, the locus of the inherited RC mutation was mapped to rat chromosomal band 10q12, near the protamine locus (logarithm of odds score = 17.96). Renal tumors also showed a loss of heterozygosity at this locus, lending support to the recessive nature of this putative tumor suppressor gene. Our result suggested that the human homolog of the RC gene may reside on human chromosome 16, not known to be altered commonly in human RC.

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Selected References

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  1. Anglard P., Tory K., Brauch H., Weiss G. H., Latif F., Merino M. J., Lerman M. I., Zbar B., Linehan W. M. Molecular analysis of genetic changes in the origin and development of renal cell carcinoma. Cancer Res. 1991 Feb 15;51(4):1071–1077. [PubMed] [Google Scholar]
  2. Cohen A. J., Li F. P., Berg S., Marchetto D. J., Tsai S., Jacobs S. C., Brown R. S. Hereditary renal-cell carcinoma associated with a chromosomal translocation. N Engl J Med. 1979 Sep 13;301(11):592–595. doi: 10.1056/NEJM197909133011107. [DOI] [PubMed] [Google Scholar]
  3. Eker R., Mossige J., Johannessen J. V., Aars H. Hereditary renal adenomas and adenocarcinomas in rats. Diagn Histopathol. 1981 Jan-Mar;4(1):99–110. [PubMed] [Google Scholar]
  4. Funaki K., Everitt J., Oshimura M., Freed J. J., Knudson A. G., Jr, Walker C. Hereditary renal cell carcinoma in the rat associated with nonrandom loss of chromosomes 5 and 6. Cancer Res. 1991 Aug 15;51(16):4415–4422. [PubMed] [Google Scholar]
  5. Gomella L. G., Sargent E. R., Wade T. P., Anglard P., Linehan W. M., Kasid A. Expression of transforming growth factor alpha in normal human adult kidney and enhanced expression of transforming growth factors alpha and beta 1 in renal cell carcinoma. Cancer Res. 1989 Dec 15;49(24 Pt 1):6972–6975. [PubMed] [Google Scholar]
  6. Himmelbauer H., Pohlschmidt M., Snarey A., Germino G. G., Weinstat-Saslow D., Somlo S., Reeders S. T., Frischauf A. M. Human-mouse homologies in the region of the polycystic kidney disease gene (PKD1). Genomics. 1992 May;13(1):35–38. doi: 10.1016/0888-7543(92)90198-2. [DOI] [PubMed] [Google Scholar]
  7. Hino O., Klein-Szanto A. J., Freed J. J., Testa J. R., Brown D. Q., Vilensky M., Yeung R. S., Tartof K. D., Knudson A. G. Spontaneous and radiation-induced renal tumors in the Eker rat model of dominantly inherited cancer. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):327–331. doi: 10.1073/pnas.90.1.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Knudson A. G., Jr Hereditary cancer, oncogenes, and antioncogenes. Cancer Res. 1985 Apr;45(4):1437–1443. [PubMed] [Google Scholar]
  9. Kovacs A., Kovacs G. Low chromosome number in chromophobe renal cell carcinomas. Genes Chromosomes Cancer. 1992 Apr;4(3):267–268. doi: 10.1002/gcc.2870040313. [DOI] [PubMed] [Google Scholar]
  10. Kovacs G., Frisch S. Clonal chromosome abnormalities in tumor cells from patients with sporadic renal cell carcinomas. Cancer Res. 1989 Feb 1;49(3):651–659. [PubMed] [Google Scholar]
  11. Latif F., Tory K., Gnarra J., Yao M., Duh F. M., Orcutt M. L., Stackhouse T., Kuzmin I., Modi W., Geil L. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993 May 28;260(5112):1317–1320. doi: 10.1126/science.8493574. [DOI] [PubMed] [Google Scholar]
  12. Levan G., Szpirer J., Szpirer C., Klinga K., Hanson C., Islam M. Q. The gene map of the Norway rat (Rattus norvegicus) and comparative mapping with mouse and man. Genomics. 1991 Jul;10(3):699–718. doi: 10.1016/0888-7543(91)90455-n. [DOI] [PubMed] [Google Scholar]
  13. Morita R., Ishikawa J., Tsutsumi M., Hikiji K., Tsukada Y., Kamidono S., Maeda S., Nakamura Y. Allelotype of renal cell carcinoma. Cancer Res. 1991 Feb 1;51(3):820–823. [PubMed] [Google Scholar]
  14. Murphree A. L., Benedict W. F. Retinoblastoma: clues to human oncogenesis. Science. 1984 Mar 9;223(4640):1028–1033. doi: 10.1126/science.6320372. [DOI] [PubMed] [Google Scholar]
  15. Nanus D. M., Mentle I. R., Motzer R. J., Bander N. H., Albino A. P. Infrequent ras oncogene point mutations in renal cell carcinoma. J Urol. 1990 Jan;143(1):175–178. doi: 10.1016/s0022-5347(17)39905-6. [DOI] [PubMed] [Google Scholar]
  16. Ogawa O., Kakehi Y., Ogawa K., Koshiba M., Sugiyama T., Yoshida O. Allelic loss at chromosome 3p characterizes clear cell phenotype of renal cell carcinoma. Cancer Res. 1991 Feb 1;51(3):949–953. [PubMed] [Google Scholar]
  17. Pathak S., Strong L. C., Ferrell R. E., Trindade A. Familial renal cell carcinoma with a 3;11 chromosome translocation limited to tumor cells. Science. 1982 Sep 3;217(4563):939–941. doi: 10.1126/science.7112106. [DOI] [PubMed] [Google Scholar]
  18. Recio L., Lane S. C., Ginsler J., Walker C. Analysis of ras DNA sequences in rat renal cell carcinoma. Mol Carcinog. 1991;4(5):350–353. doi: 10.1002/mc.2940040504. [DOI] [PubMed] [Google Scholar]
  19. Reeves R. H., Miller R. D. Mouse chromosome 16. Mamm Genome. 1992;3(Spec No):S233–S240. doi: 10.1007/BF00648434. [DOI] [PubMed] [Google Scholar]
  20. Seizinger B. R., Rouleau G. A., Ozelius L. J., Lane A. H., Farmer G. E., Lamiell J. M., Haines J., Yuen J. W., Collins D., Majoor-Krakauer D. Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature. 1988 Mar 17;332(6161):268–269. doi: 10.1038/332268a0. [DOI] [PubMed] [Google Scholar]
  21. Thoenes W., Störkel S., Rumpelt H. J., Moll R., Baum H. P., Werner S. Chromophobe cell renal carcinoma and its variants--a report on 32 cases. J Pathol. 1988 Aug;155(4):277–287. doi: 10.1002/path.1711550402. [DOI] [PubMed] [Google Scholar]
  22. Walker C., Everitt J., Freed J. J., Knudson A. G., Jr, Whiteley L. O. Altered expression of transforming growth factor-alpha in hereditary rat renal cell carcinoma. Cancer Res. 1991 Jun 1;51(11):2973–2978. [PubMed] [Google Scholar]
  23. Walker C., Goldsworthy T. L., Wolf D. C., Everitt J. Predisposition to renal cell carcinoma due to alteration of a cancer susceptibility gene. Science. 1992 Mar 27;255(5052):1693–1695. doi: 10.1126/science.1553556. [DOI] [PubMed] [Google Scholar]
  24. Yamakawa K., Morita R., Takahashi E., Hori T., Ishikawa J., Nakamura Y. A detailed deletion mapping of the short arm of chromosome 3 in sporadic renal cell carcinoma. Cancer Res. 1991 Sep 1;51(17):4707–4711. [PubMed] [Google Scholar]
  25. Yeung R. S., Taguchi T., Patriotis C., Makris A., Tsichlis P. N., Levan K. K., Levan G., Tartof K., Hino O., Knudson A. G. New markers, D16FC1 and Tp12, differentiate between rat chromosomes 16 and 17. Cytogenet Cell Genet. 1993;62(2-3):149–152. doi: 10.1159/000133459. [DOI] [PubMed] [Google Scholar]
  26. Yoshida M. A., Ohyashiki K., Ochi H., Gibas Z., Pontes J. E., Prout G. R., Jr, Huben R., Sandberg A. A. Cytogenetic studies of tumor tissue from patients with nonfamilial renal cell carcinoma. Cancer Res. 1986 Apr;46(4 Pt 2):2139–2147. [PubMed] [Google Scholar]
  27. Zbar B., Brauch H., Talmadge C., Linehan M. Loss of alleles of loci on the short arm of chromosome 3 in renal cell carcinoma. 1987 Jun 25-Jul 1Nature. 327(6124):721–724. doi: 10.1038/327721a0. [DOI] [PubMed] [Google Scholar]
  28. Zhang J., Hemschoote K., Peeters B., De Clercq N., Rombauts W., Cassiman J. J. Localization of the PRR1 gene coding for rat prostatic proline-rich polypeptides to chromosome 10 by in situ hybridization. Cytogenet Cell Genet. 1989;52(3-4):197–198. doi: 10.1159/000132877. [DOI] [PubMed] [Google Scholar]

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