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. 1989 Jun;83(6):2034–2040. doi: 10.1172/JCI114114

Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma.

A Arnold 1, H G Kim 1, R D Gaz 1, R L Eddy 1, Y Fukushima 1, M G Byers 1, T B Shows 1, H M Kronenberg 1
PMCID: PMC303928  PMID: 2723071

Abstract

Parathyroid adenomas are common benign neoplasms for which no chromosomal defects have been described. We recently found two parathyroid adenomas bearing clonal restriction fragment abnormalities involving the PTH locus, and now show that in one of these tumors: (a) a DNA rearrangement occurred at the PTH locus; (b) the rearrangement separated the PTH gene's 5' flanking region from its coding exons, conceivably placing a newly adjacent gene under the influence of PTH regulatory elements; (c) the DNA that recombined with PTH normally maps to 11q13, the known chromosomal location of several oncogenes and the gene for multiple endocrine neoplasia type I; and (d) the rearrangement was a reciprocal, conservative recombination of the locus on 11q13 (Human Gene Mapping Library assignment D11S287) with PTH (on 11p15). These data provide molecular cytogenetic evidence for the clonal occurrence of a major chromosome 11 aberrancy in this benign parathyroid tumor. The D11S287 clone could prove useful in genetic linkage analyses, in determining precise 11q13 breakpoints in other neoplasms, and in identifying a gene on chromosome 11 that may participate in parathyroid tumor development.

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Selected References

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

  1. Adelaide J., Mattei M. G., Marics I., Raybaud F., Planche J., De Lapeyriere O., Birnbaum D. Chromosomal localization of the hst oncogene and its co-amplification with the int.2 oncogene in a human melanoma. Oncogene. 1988 Apr;2(4):413–416. [PubMed] [Google Scholar]
  2. Arnold A., Cossman J., Bakhshi A., Jaffe E. S., Waldmann T. A., Korsmeyer S. J. Immunoglobulin-gene rearrangements as unique clonal markers in human lymphoid neoplasms. N Engl J Med. 1983 Dec 29;309(26):1593–1599. doi: 10.1056/NEJM198312293092601. [DOI] [PubMed] [Google Scholar]
  3. Arnold A., Staunton C. E., Kim H. G., Gaz R. D., Kronenberg H. M. Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas. N Engl J Med. 1988 Mar 17;318(11):658–662. doi: 10.1056/NEJM198803173181102. [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. Casey G., Smith R., McGillivray D., Peters G., Dickson C. Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene. Mol Cell Biol. 1986 Feb;6(2):502–510. doi: 10.1128/mcb.6.2.502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Croce C. M., Nowell P. C. Molecular basis of human B cell neoplasia. Blood. 1985 Jan;65(1):1–7. [PubMed] [Google Scholar]
  7. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  8. Friend S. H., Dryja T. P., Weinberg R. A. Oncogenes and tumor-suppressing genes. N Engl J Med. 1988 Mar 10;318(10):618–622. doi: 10.1056/NEJM198803103181007. [DOI] [PubMed] [Google Scholar]
  9. Igarashi T., Okazaki T., Potter H., Gaz R., Kronenberg H. M. Cell-specific expression of the human parathyroid hormone gene in rat pituitary cells. Mol Cell Biol. 1986 May;6(5):1830–1833. doi: 10.1128/mcb.6.5.1830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Karn J., Brenner S., Barnett L. New bacteriophage lambda vectors with positive selection for cloned inserts. Methods Enzymol. 1983;101:3–19. doi: 10.1016/0076-6879(83)01004-6. [DOI] [PubMed] [Google Scholar]
  11. Karn J., Matthes H. W., Gait M. J., Brenner S. A new selective phage cloning vector, lambda 2001, with sites for XbaI, BamHI, HindIII, EcoRI, SstI and XhoI. Gene. 1984 Dec;32(1-2):217–224. doi: 10.1016/0378-1119(84)90049-0. [DOI] [PubMed] [Google Scholar]
  12. Kovacs G., Erlandsson R., Boldog F., Ingvarsson S., Müller-Brechlin R., Klein G., Sümegi J. Consistent chromosome 3p deletion and loss of heterozygosity in renal cell carcinoma. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1571–1575. doi: 10.1073/pnas.85.5.1571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kurzrock R., Gutterman J. U., Talpaz M. The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med. 1988 Oct 13;319(15):990–998. doi: 10.1056/NEJM198810133191506. [DOI] [PubMed] [Google Scholar]
  14. Larsson C., Skogseid B., Oberg K., Nakamura Y., Nordenskjöld M. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature. 1988 Mar 3;332(6159):85–87. doi: 10.1038/332085a0. [DOI] [PubMed] [Google Scholar]
  15. Le Beau M. M. Chromosomal fragile sites and cancer-specific rearrangements. Blood. 1986 Apr;67(4):849–858. [PubMed] [Google Scholar]
  16. Nakai H., Byers M. G., Shows T. B., Taggart R. T. Assignment of the pepsinogen gene complex (PGA) to human chromosome region 11q13 by in situ hybridization. Cytogenet Cell Genet. 1986;43(3-4):215–217. doi: 10.1159/000132324. [DOI] [PubMed] [Google Scholar]
  17. Naylor S. L., Sakaguchi A. Y., Shows T. B., Law M. L., Goeddel D. V., Gray P. W. Human immune interferon gene is located on chromosome 12. J Exp Med. 1983 Mar 1;157(3):1020–1027. doi: 10.1084/jem.157.3.1020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sait S. N., Dal Cin P., Sandberg A. A. Recurrent involvement of 11q13 in acute nonlymphocytic leukemia. Cancer Genet Cytogenet. 1987 Jun;26(2):351–354. doi: 10.1016/0165-4608(87)90069-0. [DOI] [PubMed] [Google Scholar]
  19. Sandberg A. A., Turc-Carel C. The cytogenetics of solid tumors. Relation to diagnosis, classification and pathology. Cancer. 1987 Feb 1;59(3):387–395. doi: 10.1002/1097-0142(19870201)59:3<387::aid-cncr2820590306>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  20. Seizinger B. R., de la Monte S., Atkins L., Gusella J. F., Martuza R. L. Molecular genetic approach to human meningioma: loss of genes on chromosome 22. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5419–5423. doi: 10.1073/pnas.84.15.5419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shows T. B., Brown J. A., Haley L. L., Byers M. G., Eddy R. L., Cooper E. S., Goggin A. P. Assignment of the beta-glucuronidase structural gene to the pter leads to q22 region of chromosome 7 in man. Cytogenet Cell Genet. 1978;21(1-2):99–104. doi: 10.1159/000130882. [DOI] [PubMed] [Google Scholar]
  22. Shows T. B. Human genome organization of enzyme loci and metabolic diseases. Isozymes Curr Top Biol Med Res. 1983;10:323–339. [PubMed] [Google Scholar]
  23. Shows T. B., Sakaguchi A. Y., Naylor S. L. Mapping the human genome, cloned genes, DNA polymorphisms, and inherited disease. Adv Hum Genet. 1982;12:341–452. doi: 10.1007/978-1-4615-8315-8_5. [DOI] [PubMed] [Google Scholar]
  24. Shows T., Eddy R., Haley L., Byers M., Henry M., Fujita T., Matsui H., Taniguchi T. Interleukin 2 (IL2) is assigned to human chromosome 4. Somat Cell Mol Genet. 1984 May;10(3):315–318. doi: 10.1007/BF01535253. [DOI] [PubMed] [Google Scholar]
  25. Tsujimoto Y., Yunis J., Onorato-Showe L., Erikson J., Nowell P. C., Croce C. M. Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11;14) chromosome translocation. Science. 1984 Jun 29;224(4656):1403–1406. doi: 10.1126/science.6610211. [DOI] [PubMed] [Google Scholar]
  26. Whang-Peng J., Kao-Shan C. S., Lee E. C., Bunn P. A., Carney D. N., Gazdar A. F., Minna J. D. Specific chromosome defect associated with human small-cell lung cancer; deletion 3p(14-23). Science. 1982 Jan 8;215(4529):181–182. doi: 10.1126/science.6274023. [DOI] [PubMed] [Google Scholar]
  27. Yoshida T., Miyagawa K., Odagiri H., Sakamoto H., Little P. F., Terada M., Sugimura T. Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2-encoded protein. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7305–7309. doi: 10.1073/pnas.84.20.7305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yoshida T., Sakamoto H., Miyagawa K., Little P. F., Terada M., Sugimura T. Genomic clone of hst with transforming activity from a patient with acute leukemia. Biochem Biophys Res Commun. 1987 Feb 13;142(3):1019–1024. doi: 10.1016/0006-291x(87)91516-6. [DOI] [PubMed] [Google Scholar]
  29. Zabel B. U., Kronenberg H. M., Bell G. I., Shows T. B. Chromosome mapping of genes on the short arm of human chromosome 11: parathyroid hormone gene is at 11p15 together with the genes for insulin, c-Harvey-ras 1, and beta-hemoglobin. Cytogenet Cell Genet. 1985;39(3):200–205. doi: 10.1159/000132135. [DOI] [PubMed] [Google Scholar]

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