Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Nov;87(22):8751–8755. doi: 10.1073/pnas.87.22.8751

Allelic loss of chromosomes 16q and 10q in human prostate cancer.

B S Carter 1, C M Ewing 1, W S Ward 1, B F Treiger 1, T W Aalders 1, J A Schalken 1, J I Epstein 1, W B Isaacs 1
PMCID: PMC55037  PMID: 1978938

Abstract

Recent advances in understanding the molecular genetics of common adult tumors have indicated that multiple genetic alterations including the activation of oncogenes and the inactivation of tumor suppressor genes are important in the pathogenesis of these tumors. Loss of heterozygosity is a hallmark of tumor suppressor gene inactivation and has been used to identify chromosomal regions that contain these genes. We have examined allelic loss in the most common tumor in men, prostate cancer. Twenty-eight prostate cancer specimens have been examined for loss of heterozygosity at 11 different chromosomal arms including 3p, 7q, 9q, 10p, 10q, 11p, 13q, 16p, 16q, 17p, and 18q. Fifty-four percent (13/24) of clinically localized tumors and 4 of 4 metastatic tumors showed loss of heterozygosity on at least one chromosome. Chromosomes 16q and 10q exhibited the highest frequency of loss of heterozygosity with 30% of tumors showing loss at these chromosomes. These data demonstrate that allelic loss is a common event in prostate cancer and suggest that chromosomes 16q and 10q may contain the sites of tumor suppressor genes important in the pathogenesis of human prostate cancer.

Full text

PDF
8753

Images in this article

8753Image
on p.8753
8753Image
on p.8753
8753Image
on p.8753
8753Image
on p.8753

Selected References

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

  1. Atkin N. B., Baker M. C. Chromosome study of five cancers of the prostate. Hum Genet. 1985;70(4):359–364. doi: 10.1007/BF00295378. [DOI] [PubMed] [Google Scholar]
  2. Baker S. J., Fearon E. R., Nigro J. M., Hamilton S. R., Preisinger A. C., Jessup J. M., vanTuinen P., Ledbetter D. H., Barker D. F., Nakamura Y. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science. 1989 Apr 14;244(4901):217–221. doi: 10.1126/science.2649981. [DOI] [PubMed] [Google Scholar]
  3. Bookstein R., Shew J. Y., Chen P. L., Scully P., Lee W. H. Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene. Science. 1990 Feb 9;247(4943):712–715. doi: 10.1126/science.2300823. [DOI] [PubMed] [Google Scholar]
  4. Bos J. L., Fearon E. R., Hamilton S. R., Verlaan-de Vries M., van Boom J. H., van der Eb A. J., Vogelstein B. Prevalence of ras gene mutations in human colorectal cancers. 1987 May 28-Jun 3Nature. 327(6120):293–297. doi: 10.1038/327293a0. [DOI] [PubMed] [Google Scholar]
  5. Bragg T., Nakamura Y., Jones C., White R. Isolation and mapping of a polymorphic DNA sequence (cTBQ7) on chromosome 10 [D10S28]. Nucleic Acids Res. 1988 Dec 9;16(23):11395–11395. doi: 10.1093/nar/16.23.11395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brothman A. R., Peehl D. M., Patel A. M., McNeal J. E. Frequency and pattern of karyotypic abnormalities in human prostate cancer. Cancer Res. 1990 Jun 15;50(12):3795–3803. [PubMed] [Google Scholar]
  7. Bufton L., Mohandas T. K., Magenis R. E., Sheehy R., Bestwick R. K., Litt M. A highly polymorphic locus on chromosome 16q revealed by a probe from a chromosome-specific cosmid library. Hum Genet. 1986 Dec;74(4):425–431. doi: 10.1007/BF00280499. [DOI] [PubMed] [Google Scholar]
  8. Call K. M., Glaser T., Ito C. Y., Buckler A. J., Pelletier J., Haber D. A., Rose E. A., Kral A., Yeger H., Lewis W. H. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell. 1990 Feb 9;60(3):509–520. doi: 10.1016/0092-8674(90)90601-a. [DOI] [PubMed] [Google Scholar]
  9. Callahan R., Campbell G. Mutations in human breast cancer: an overview. J Natl Cancer Inst. 1989 Dec 6;81(23):1780–1786. doi: 10.1093/jnci/81.23.1780. [DOI] [PubMed] [Google Scholar]
  10. Cavenee W. K., Dryja T. P., Phillips R. A., Benedict W. F., Godbout R., Gallie B. L., Murphree A. L., Strong L. C., White R. L. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. 1983 Oct 27-Nov 2Nature. 305(5937):779–784. doi: 10.1038/305779a0. [DOI] [PubMed] [Google Scholar]
  11. Cawthon R. M., Weiss R., Xu G. F., Viskochil D., Culver M., Stevens J., Robertson M., Dunn D., Gesteland R., O'Connell P. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell. 1990 Jul 13;62(1):193–201. doi: 10.1016/0092-8674(90)90253-b. [DOI] [PubMed] [Google Scholar]
  12. Fearon E. R., Cho K. R., Nigro J. M., Kern S. E., Simons J. W., Ruppert J. M., Hamilton S. R., Preisinger A. C., Thomas G., Kinzler K. W. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science. 1990 Jan 5;247(4938):49–56. doi: 10.1126/science.2294591. [DOI] [PubMed] [Google Scholar]
  13. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  14. Friend S. H., Bernards R., Rogelj S., Weinberg R. A., Rapaport J. M., Albert D. M., Dryja T. P. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 1986 Oct 16;323(6089):643–646. doi: 10.1038/323643a0. [DOI] [PubMed] [Google Scholar]
  15. Gessler M., Poustka A., Cavenee W., Neve R. L., Orkin S. H., Bruns G. A. Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature. 1990 Feb 22;343(6260):774–778. doi: 10.1038/343774a0. [DOI] [PubMed] [Google Scholar]
  16. Gibas Z., Becher R., Kawinski E., Horoszewicz J., Sandberg A. A. A high-resolution study of chromosome changes in a human prostatic carcinoma cell line (LNCaP). Cancer Genet Cytogenet. 1984 Apr;11(4):399–404. doi: 10.1016/0165-4608(84)90020-7. [DOI] [PubMed] [Google Scholar]
  17. Goelz S. E., Hamilton S. R., Vogelstein B. Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. Biochem Biophys Res Commun. 1985 Jul 16;130(1):118–126. doi: 10.1016/0006-291x(85)90390-0. [DOI] [PubMed] [Google Scholar]
  18. Harris P., Lalande M., Stroh H., Bruns G., Flint A., Latt S. A. Construction of a chromosome 16-enriched phage library and characterization of several DNA segments from 16p. Hum Genet. 1987 Oct;77(2):95–103. doi: 10.1007/BF00272372. [DOI] [PubMed] [Google Scholar]
  19. Hoff M., Nakamura Y., Payson R., O'Connell P., Leppert M., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence pMHZ15 on chromosome 10 [D10S17]. Nucleic Acids Res. 1988 Jan 11;16(1):373–373. doi: 10.1093/nar/16.1.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Huang H. J., Yee J. K., Shew J. Y., Chen P. L., Bookstein R., Friedmann T., Lee E. Y., Lee W. H. Suppression of the neoplastic phenotype by replacement of the RB gene in human cancer cells. Science. 1988 Dec 16;242(4885):1563–1566. doi: 10.1126/science.3201247. [DOI] [PubMed] [Google Scholar]
  21. Iizumi T., Yazaki T., Kanoh S., Kondo I., Koiso K. Establishment of a new prostatic carcinoma cell line (TSU-Pr1). J Urol. 1987 Jun;137(6):1304–1306. doi: 10.1016/s0022-5347(17)44488-0. [DOI] [PubMed] [Google Scholar]
  22. James C. D., Carlbom E., Dumanski J. P., Hansen M., Nordenskjold M., Collins V. P., Cavenee W. K. Clonal genomic alterations in glioma malignancy stages. Cancer Res. 1988 Oct 1;48(19):5546–5551. [PubMed] [Google Scholar]
  23. Kagan J., Finan J., Letofsky J., Besa E. C., Nowell P. C., Croce C. M. Alpha-chain locus of the T-cell antigen receptor is involved in the t(10;14) chromosome translocation of T-cell acute lymphocytic leukemia. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4543–4546. doi: 10.1073/pnas.84.13.4543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kern S. E., Fearon E. R., Tersmette K. W., Enterline J. P., Leppert M., Nakamura Y., White R., Vogelstein B., Hamilton S. R. Clinical and pathological associations with allelic loss in colorectal carcinoma [corrected]. JAMA. 1989 Jun 2;261(21):3099–3103. doi: 10.1001/jama.261.21.3099. [DOI] [PubMed] [Google Scholar]
  25. König J. J., Hagemeijer A., Smit B., Kamst E., Romijn J. C., Schröder F. H. Cytogenetic characterization of an established xenografted prostatic adenocarcinoma cell line (PC-82). Cancer Genet Cytogenet. 1988 Aug;34(1):91–99. doi: 10.1016/0165-4608(88)90173-2. [DOI] [PubMed] [Google Scholar]
  26. Lee S. E., Currin S. M., Paulson D. F., Walther P. J. Flow cytometric determination of ploidy in prostatic adenocarcinoma: a comparison with seminal vesicle involvement and histopathological grading as a predictor of clinical recurrence. J Urol. 1988 Oct;140(4):769–774. doi: 10.1016/s0022-5347(17)41808-8. [DOI] [PubMed] [Google Scholar]
  27. Litt M., Mueller O. T., Shows T. B., Litt R. A single copy subclone, p1-101, from cosmid 3-3B, defines three RFLPs on 10pter-q23 [HGM9 no. D10S4]. Nucleic Acids Res. 1987 Mar 25;15(6):2783–2783. doi: 10.1093/nar/15.6.2783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Maeda N., Yang F., Barnett D. R., Bowman B. H., Smithies O. Duplication within the haptoglobin Hp2 gene. Nature. 1984 May 10;309(5964):131–135. doi: 10.1038/309131a0. [DOI] [PubMed] [Google Scholar]
  29. Nakamura Y., Fujimoto E., O'Connell P., Leppert M., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence pEFD126.3 on chromosome 9q (D9S7). Nucleic Acids Res. 1987 Dec 23;15(24):10607–10607. doi: 10.1093/nar/15.24.10607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nakamura Y., Hoff M., Ballard L., O'Connell P., Leppert M., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence (cMHZ47) on chromosome 13 [D13S52]. Nucleic Acids Res. 1988 Apr 11;16(7):3119–3119. doi: 10.1093/nar/16.7.3119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nakamura Y., Lathrop M., Bragg T., Leppert M., O'Connell P., Jones C., Lalouel J. M., White R. An extended genetic linkage map of markers for human chromosome 10. Genomics. 1988 Nov;3(4):389–392. doi: 10.1016/0888-7543(88)90133-4. [DOI] [PubMed] [Google Scholar]
  32. Parmiter A. H., Balaban G., Clark W. H., Jr, Nowell P. C. Possible involvement of the chromosome region 10q24----q26 in early stages of melanocytic neoplasia. Cancer Genet Cytogenet. 1988 Feb;30(2):313–317. doi: 10.1016/0165-4608(88)90200-2. [DOI] [PubMed] [Google Scholar]
  33. Ramesh V., Benoit L. A., Crawford P., Harvey P. T., Shows T. B., Shih V. E., Gusella J. F. The ornithine aminotransferase (OAT) locus: analysis of RFLPs in gyrate atrophy. Am J Hum Genet. 1988 Feb;42(2):365–372. [PMC free article] [PubMed] [Google Scholar]
  34. Ritchie A. W., Dorey F., Layfield L. J., Hannah J., Lovrekovich H., deKernion J. B. Relationship of DNA content to conventional prognostic factors in clinically localised carcinoma of the prostate. Br J Urol. 1988 Sep;62(3):245–260. doi: 10.1111/j.1464-410x.1988.tb04329.x. [DOI] [PubMed] [Google Scholar]
  35. Schwartz C. E., Johnson J. P., Holycross B., Mandeville T. M., Sears T. S., Graul E. A., Carey J. C., Schroer R. J., Phelan M. C., Szollar J. Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome. Am J Hum Genet. 1988 Nov;43(5):597–604. [PMC free article] [PubMed] [Google Scholar]
  36. Sebastio G., Riccio A., Verde P., Scarpato N., Blasi F. BamHI RFLP linked to the human urokinase gene. Nucleic Acids Res. 1985 Jul 25;13(14):5404–5404. doi: 10.1093/nar/13.14.5404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Shih C., Weinberg R. A. Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell. 1982 May;29(1):161–169. doi: 10.1016/0092-8674(82)90100-3. [DOI] [PubMed] [Google Scholar]
  38. Tsai Y. C., Nichols P. W., Hiti A. L., Williams Z., Skinner D. G., Jones P. A. Allelic losses of chromosomes 9, 11, and 17 in human bladder cancer. Cancer Res. 1990 Jan 1;50(1):44–47. [PubMed] [Google Scholar]
  39. Tsuda H., Zhang W. D., Shimosato Y., Yokota J., Terada M., Sugimura T., Miyamura T., Hirohashi S. Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6791–6794. doi: 10.1073/pnas.87.17.6791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]
  41. Vogelstein B., Fearon E. R., Kern S. E., Hamilton S. R., Preisinger A. C., Nakamura Y., White R. Allelotype of colorectal carcinomas. Science. 1989 Apr 14;244(4901):207–211. doi: 10.1126/science.2565047. [DOI] [PubMed] [Google Scholar]
  42. Wallace M. R., Marchuk D. A., Andersen L. B., Letcher R., Odeh H. M., Saulino A. M., Fountain J. W., Brereton A., Nicholson J., Mitchell A. L. Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science. 1990 Jul 13;249(4965):181–186. doi: 10.1126/science.2134734. [DOI] [PubMed] [Google Scholar]
  43. Weston A., Willey J. C., Modali R., Sugimura H., McDowell E. M., Resau J., Light B., Haugen A., Mann D. L., Trump B. F. Differential DNA sequence deletions from chromosomes 3, 11, 13, and 17 in squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma of the human lung. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5099–5103. doi: 10.1073/pnas.86.13.5099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wiggs J., Nordenskjöld M., Yandell D., Rapaport J., Grondin V., Janson M., Werelius B., Petersen R., Craft A., Riedel K. Prediction of the risk of hereditary retinoblastoma, using DNA polymorphisms within the retinoblastoma gene. N Engl J Med. 1988 Jan 21;318(3):151–157. doi: 10.1056/NEJM198801213180305. [DOI] [PubMed] [Google Scholar]
  45. Wong Z., Wilson V., Jeffreys A. J., Thein S. L. Cloning a selected fragment from a human DNA 'fingerprint': isolation of an extremely polymorphic minisatellite. Nucleic Acids Res. 1986 Jun 11;14(11):4605–4616. doi: 10.1093/nar/14.11.4605. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES