Skip to main content
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
. 1986 Feb;83(4):1031–1035. doi: 10.1073/pnas.83.4.1031

Amplification units containing human N-myc and c-myc genes.

K W Kinzler, B A Zehnbauer, G M Brodeur, R C Seeger, J M Trent, P S Meltzer, B Vogelstein
PMCID: PMC323004  PMID: 3006024

Abstract

The amplification units in human tumors containing amplified myc genes were examined. The amplification unit in all cases consisted of a large genomic region coamplified with the coding region of the myc genes themselves. In eight independent neuroblastomas containing N-myc amplifications, the amplification unit was estimated to be 290 to 430 kilobases. This amplification unit was highly conserved among the different neuroblastomas, with some neuroblastomas containing almost identical units. In contrast, five tumor cell lines containing c-myc amplifications exhibited amplification units that were more variable in size (90 to 300 kilobases) and sequence content; at least three different patterns of c-myc amplification units could be discerned.

Full text

PDF
1031

Images in this article

Selected References

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

  1. Alitalo K., Schwab M., Lin C. C., Varmus H. E., Bishop J. M. Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1707–1711. doi: 10.1073/pnas.80.6.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alitalo K., Winqvist R., Lin C. C., de la Chapelle A., Schwab M., Bishop J. M. Aberrant expression of an amplified c-myb oncogene in two cell lines from a colon carcinoma. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4534–4538. doi: 10.1073/pnas.81.14.4534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ardeshir F., Giulotto E., Zieg J., Brison O., Liao W. S., Stark G. R. Structure of amplified DNA in different Syrian hamster cell lines resistant to N-(phosphonacetyl)-L-aspartate. Mol Cell Biol. 1983 Nov;3(11):2076–2088. doi: 10.1128/mcb.3.11.2076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blair D. G., Oskarsson M., Wood T. G., McClements W. L., Fischinger P. J., Vande Woude G. G. Activation of the transforming potential of a normal cell sequence: a molecular model for oncogenesis. Science. 1981 May 22;212(4497):941–943. doi: 10.1126/science.7233190. [DOI] [PubMed] [Google Scholar]
  5. Bostock C. J., Tyler-Smith C. Gene amplification in methotrexate-resistant mouse cells. II. Rearrangement and amplification of non-dihydrofolate reductase gene sequences accompany chromosomal changes. J Mol Biol. 1981 Dec 5;153(2):219–236. doi: 10.1016/0022-2836(81)90275-8. [DOI] [PubMed] [Google Scholar]
  6. Brodeur G. M., Seeger R. C., Schwab M., Varmus H. E., Bishop J. M. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science. 1984 Jun 8;224(4653):1121–1124. doi: 10.1126/science.6719137. [DOI] [PubMed] [Google Scholar]
  7. Collins S. J., Groudine M. T. Rearrangement and amplification of c-abl sequences in the human chronic myelogenous leukemia cell line K-562. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4813–4817. doi: 10.1073/pnas.80.15.4813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Collins S., Groudine M. Amplification of endogenous myc-related DNA sequences in a human myeloid leukaemia cell line. Nature. 1982 Aug 12;298(5875):679–681. doi: 10.1038/298679a0. [DOI] [PubMed] [Google Scholar]
  9. Dalla-Favera R., Wong-Staal F., Gallo R. C. Onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient. Nature. 1982 Sep 2;299(5878):61–63. doi: 10.1038/299061a0. [DOI] [PubMed] [Google Scholar]
  10. DeFeo D., Gonda M. A., Young H. A., Chang E. H., Lowy D. R., Scolnick E. M., Ellis R. W. Analysis of two divergent rat genomic clones homologous to the transforming gene of Harvey murine sarcoma virus. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3328–3332. doi: 10.1073/pnas.78.6.3328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Federspiel N. A., Beverley S. M., Schilling J. W., Schimke R. T. Novel DNA rearrangements are associated with dihydrofolate reductase gene amplification. J Biol Chem. 1984 Jul 25;259(14):9127–9140. [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Gross-Bellard M., Oudet P., Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem. 1973 Jul 2;36(1):32–38. doi: 10.1111/j.1432-1033.1973.tb02881.x. [DOI] [PubMed] [Google Scholar]
  15. Kanda N., Schreck R., Alt F., Bruns G., Baltimore D., Latt S. Isolation of amplified DNA sequences from IMR-32 human neuroblastoma cells: facilitation by fluorescence-activated flow sorting of metaphase chromosomes. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4069–4073. doi: 10.1073/pnas.80.13.4069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kirsch I. R., Ravetch J. V., Kwan S. P., Max E. E., Ney R. L., Leder P. Multiple immunoglobulin switch region homologies outside the heavy chain constant region locus. Nature. 1981 Oct 15;293(5833):585–587. doi: 10.1038/293585a0. [DOI] [PubMed] [Google Scholar]
  17. Kohl N. E., Gee C. E., Alt F. W. Activated expression of the N-myc gene in human neuroblastomas and related tumors. Science. 1984 Dec 14;226(4680):1335–1337. doi: 10.1126/science.6505694. [DOI] [PubMed] [Google Scholar]
  18. Kohl N. E., Kanda N., Schreck R. R., Bruns G., Latt S. A., Gilbert F., Alt F. W. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell. 1983 Dec;35(2 Pt 1):359–367. doi: 10.1016/0092-8674(83)90169-1. [DOI] [PubMed] [Google Scholar]
  19. Kozbor D., Croce C. M. Amplification of the c-myc oncogene in one of five human breast carcinoma cell lines. Cancer Res. 1984 Feb;44(2):438–441. [PubMed] [Google Scholar]
  20. Lee W. H., Murphree A. L., Benedict W. F. Expression and amplification of the N-myc gene in primary retinoblastoma. 1984 May 31-Jun 6Nature. 309(5967):458–460. doi: 10.1038/309458a0. [DOI] [PubMed] [Google Scholar]
  21. Libermann T. A., Nusbaum H. R., Razon N., Kris R., Lax I., Soreq H., Whittle N., Waterfield M. D., Ullrich A., Schlessinger J. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985 Jan 10;313(5998):144–147. doi: 10.1038/313144a0. [DOI] [PubMed] [Google Scholar]
  22. Lin C. R., Chen W. S., Kruiger W., Stolarsky L. S., Weber W., Evans R. M., Verma I. M., Gill G. N., Rosenfeld M. G. Expression cloning of human EGF receptor complementary DNA: gene amplification and three related messenger RNA products in A431 cells. Science. 1984 May 25;224(4651):843–848. doi: 10.1126/science.6326261. [DOI] [PubMed] [Google Scholar]
  23. Little C. D., Nau M. M., Carney D. N., Gazdar A. F., Minna J. D. Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature. 1983 Nov 10;306(5939):194–196. doi: 10.1038/306194a0. [DOI] [PubMed] [Google Scholar]
  24. Merlino G. T., Xu Y. H., Ishii S., Clark A. J., Semba K., Toyoshima K., Yamamoto T., Pastan I. Amplification and enhanced expression of the epidermal growth factor receptor gene in A431 human carcinoma cells. Science. 1984 Apr 27;224(4647):417–419. doi: 10.1126/science.6200934. [DOI] [PubMed] [Google Scholar]
  25. Michitsch R. W., Montgomery K. T., Melera P. W. Expression of the amplified domain in human neuroblastoma cells. Mol Cell Biol. 1984 Nov;4(11):2370–2380. doi: 10.1128/mcb.4.11.2370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Milbrandt J. D., Heintz N. H., White W. C., Rothman S. M., Hamlin J. L. Methotrexate-resistant Chinese hamster ovary cells have amplified a 135-kilobase-pair region that includes the dihydrofolate reductase gene. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6043–6047. doi: 10.1073/pnas.78.10.6043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Montoya-Zavala M., Hamlin J. L. Similar 150-kilobase DNA sequences are amplified in independently derived methotrexate-resistant Chinese hamster cells. Mol Cell Biol. 1985 Apr;5(4):619–627. doi: 10.1128/mcb.5.4.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nunberg J. H., Kaufman R. J., Schimke R. T., Urlaub G., Chasin L. A. Amplified dihydrofolate reductase genes are localized to a homogeneously staining region of a single chromosome in a methotrexate-resistant Chinese hamster ovary cell line. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5553–5556. doi: 10.1073/pnas.75.11.5553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pelicci P. G., Lanfrancone L., Brathwaite M. D., Wolman S. R., Dalla-Favera R. Amplification of the c-myb oncogene in a case of human acute myelogenous leukemia. Science. 1984 Jun 8;224(4653):1117–1121. doi: 10.1126/science.6585957. [DOI] [PubMed] [Google Scholar]
  30. Roninson I. B., Abelson H. T., Housman D. E., Howell N., Varshavsky A. Amplification of specific DNA sequences correlates with multi-drug resistance in Chinese hamster cells. Nature. 1984 Jun 14;309(5969):626–628. doi: 10.1038/309626a0. [DOI] [PubMed] [Google Scholar]
  31. Roninson I. B. Detection and mapping of homologous, repeated and amplified DNA sequences by DNA renaturation in agarose gels. Nucleic Acids Res. 1983 Aug 25;11(16):5413–5431. doi: 10.1093/nar/11.16.5413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schimke R. T. Gene amplification in cultured animal cells. Cell. 1984 Jul;37(3):705–713. doi: 10.1016/0092-8674(84)90406-9. [DOI] [PubMed] [Google Scholar]
  33. Schwab M., Alitalo K., Klempnauer K. H., Varmus H. E., Bishop J. M., Gilbert F., Brodeur G., Goldstein M., Trent J. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature. 1983 Sep 15;305(5931):245–248. doi: 10.1038/305245a0. [DOI] [PubMed] [Google Scholar]
  34. Selden J. R., Emanuel B. S., Wang E., Cannizzaro L., Palumbo A., Erikson J., Nowell P. C., Rovera G., Croce C. M. Amplified C lambda and c-abl genes are on the same marker chromosome in K562 leukemia cells. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7289–7292. doi: 10.1073/pnas.80.23.7289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Shiloh Y., Shipley J., Brodeur G. M., Bruns G., Korf B., Donlon T., Schreck R. R., Seeger R., Sakai K., Latt S. A. Differential amplification, assembly, and relocation of multiple DNA sequences in human neuroblastomas and neuroblastoma cell lines. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3761–3765. doi: 10.1073/pnas.82.11.3761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stark G. R., Wahl G. M. Gene amplification. Annu Rev Biochem. 1984;53:447–491. doi: 10.1146/annurev.bi.53.070184.002311. [DOI] [PubMed] [Google Scholar]
  37. Trent J., Meltzer P., Rosenblum M., Harsh G., Kinzler K., Mashal R., Feinberg A., Vogelstein B. Evidence for rearrangement, amplification, and expression of c-myc in a human glioblastoma. Proc Natl Acad Sci U S A. 1986 Jan;83(2):470–473. doi: 10.1073/pnas.83.2.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Varshavsky A. On the possibility of metabolic control of replicon "misfiring": relationship to emergence of malignant phenotypes in mammalian cell lineages. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3673–3677. doi: 10.1073/pnas.78.6.3673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wahl G. M., Vitto L., Padgett R. A., Stark G. R. Single-copy and amplified CAD genes in Syrian hamster chromosomes localized by a highly sensitive method for in situ hybridization. Mol Cell Biol. 1982 Mar;2(3):308–319. doi: 10.1128/mcb.2.3.308. [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