Skip to main content
SpringerLink
Log in

Loss of heterozygosity of the L-myc oncogene in human breast tumors

  • Original Investigations
  • Published:
Human Genetics Aims and scope Submit manuscript

Summary

Recent studies suggest that loss of heterozygosity may play an important role in various human neoplasia. Cytogenetic abnormalities detected in primary breast tumors led us to examine breast tumor DNAs for deletions. In the present study, we demonstrate, using restriction fragment length polymorphism (RFLP) analysis at the L-myc proto-oncogene (chromosome 1p32), a frequent loss of heterozygosity in primary breast tumor DNAs (55 out of 152 informative tumor DNAs). Most of these deletions appear to be limited to chromosome 1p. No correlation was observed between this genetic alteration and several parameters of each patient's history or characteristics of the tumor. However, a significantly (P = 0.011) shorter survival period after relapse was observed for patients with loss of heterozygosity at L-myc in primary tumor DNAs compared with patients with tumor DNAs lacking this alteration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ali IU, Lidereau R, Theillet C, Callahan R (1987) Reduction to homozygosity of genes on chromosome 11 in human breast neoplasia. Science 238:185–188

    Google Scholar 

  • Ali IU, Lidereau R, Callahan R (1989) Presence of two members of c-erbA receptor gene family (c-erbAβ and c-erbA2) in smallest region of somatic homozygosity on chromosome 3p21-p25 in human breast carcinoma. J Natl Cancer Inst 81:1815–1820

    Google Scholar 

  • Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, Van Tuinen P, Ledbetter DH, Barker DF, Nakamura Y, White R, Vogelstein B (1989) Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244:217–221

    Google Scholar 

  • Benedict WF, Weissman BE, Mark C, Stranbridge EJ (1984) Tumorigenicity of human HT 1080 fibrosarcoma X normal fibroblast hybrids: chromosome dosage dependency. Cancer 44:3471–3479

    Google Scholar 

  • Brauch H, Johnson B, Hovis J, Takahiko Y, Gazqar A, Pettengill OS, Graziano S, Sorensen GD, Poiesz BJ, Minna J, Linehan M, Zbar B (1987) Molecular analysis of the short arm of chromosome 3 in small-cell and non-small-cell carcinoma of the lung. N Engl J Med 317:1109–1113

    Google Scholar 

  • Callahan R, Ali IU, Hacene K, Brunet M, Lidereau R (1989) The current status of int genes, proto-oncogenes, and recessive mutations in primary human breast tumors: their potential usefulness in prognosis. In: Rich MA, Hager JC, Keydar L (eds) Breast cancer: progress in biology, clinical management and prevention. Kluwer, Dordrecht, pp 27–40

    Google Scholar 

  • Chen LC, Dollbaum C, Smith HS (1989) Loss of heterozygosity on chromosome 1q in human breast cancer. Proc Natl Acad Sci USA 86:7204–7207

    Google Scholar 

  • Cruciger QV, Pathak S, Cailleau R (1976) Human breast carcinomas: marker chromosomes involving 1q in seven cases. Cytogenet Cell Genet 17:231–235

    Google Scholar 

  • Dracopoli NC, Stranger BZ, Lager M, Housman DE (1988) Localisation of the FGR proto-oncogene on the genetic linkage map of human chromosome 1p. Genomics 3:124–128

    Google Scholar 

  • Escot C, Theillet C, Lidereau R, Spyratos F, Champeme MH, Gest J, Callahan R (1986) Genetic alteration of the c-myc protooncogene (MYC) in human primary breast carcinomas. Proc Natl Acad Sci USA 83:4834–4838

    Google Scholar 

  • Ferti-Passantonopoulou AD, Panani AD (1987) Common cytogenetic findings in primary breast cancer. Cancer Genet Cytogenet 27:289–298

    Google Scholar 

  • Fey MF, Hesketh C, Wainscoat JS, Gendler S, Thein SL (1989) Clonal allele loss in gastrointestinal cancers. Br J Cancer 59:750–754

    Google Scholar 

  • Gebhart E, Brüderlein S, Augustus M, Siebert E, Feldner J, Schmidt W (1986) Cytogenetic studies on human breast carcinomas. Breast Cancer Res Treat 8:125–138

    Google Scholar 

  • Gendler S, Tailor-Papadimitriou J, Duhig T, Rothbard J, Burchell J (1988) A highly immunogenic region of a human polymorphic epithelial mucin expressed by carcinomas is made up of tandem repeats. J Biol Chem 263:12820–12823

    Google Scholar 

  • Genuardi M, Tsihira H, Anderson DE, Saunders GF (1989) Distal deletion of chromosome 1p in ductal carcinoma of the breast. Am J Hum Genet 45:73–82

    Google Scholar 

  • Gilbert F, Feder M, Baladan G, Brangman D, Lurie DK, Podolsky R, Rinaldt V, Vinikoor N, Weisband J (1984) Human neuroblastomas and abnormalities of chromosome 1 and 17. Cancer Res 44:5444–5449

    Google Scholar 

  • Hattori K, Angel P, Le Beau MM, Karin M (1988) Structure and chromosomal localization of the functional intronless human JUN proto-oncogene. Proc Natl Acad Sci USA 85:9148–9152

    Google Scholar 

  • Johnson BE, Ihde DC, Makuch RW, Gazdar AF, Carmay DN, Oie H, Russel E, Nau MM, Minna JD (1987) Myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course. J Clin Invest 79:1629–1634

    Google Scholar 

  • Knudson AG (1989) Hereditary cancers: clues to mechanisms of carcinogenesis. Br J Cancer 59:661–666

    Google Scholar 

  • Kovacs G, Erlandsson R, Boldog F, Ingvarsson F, MüllerBrechlin R, Klein G, Sümegi J (1988) Consistent chromosome 3p deletion and loss of heterozygosity in renal cell carcinoma. Proc Natl Acad Sci USA 85:1571–1575

    Google Scholar 

  • Larsson C, Skogseid B, Oberg K, Nakamura Y, Nordenskjold M (1988) Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 332:85–87

    Google Scholar 

  • Lee EYHP, To H, Shew JY, Bookstein R, Scully P, Lee WH (1988) Inactivation of the retinoblastoma susceptibility gene in human breast cancers. Science 241:218–221

    Google Scholar 

  • Leppert M, Dobbs M, Scambler P, O'Connell P, Nakamura Y, Stauffer D, Woodward S, Burt R, Hugues J, Gardner E, Lathrop M, Wasmuth J, Lalouel JM, White R (1987) The gene for familial polyposis coli maps to the long arm of chromosome 5. Science 238:1411–1413

    Google Scholar 

  • Lundberg C, Skoog L, Cavenee WK, Nordenskjold M (1987) Loss of heterozygosity in human ductal breast tumors indicates a recessive mutation on chromosome 13. Proc Natl Acad Sci USA 84:2372–2376

    Google Scholar 

  • Mackay J, Elder PA, Porteous DJ, Steel CM, Hawkins RA, Goings JJ, Chetty U (1988a) Partial deletion of chromosome 11p in breast cancer correlates with size of primary tumour and oestrogen receptor level. Br J Cancer 58:710–714

    Google Scholar 

  • Mackay J, Steel CM, Elder PA, Forrest APM, Evans HJ (1988b) Allele loss on short arm of chromosome 17 in breast cancers. Lancet II:1384–1385

    Google Scholar 

  • Mathew CGP, Smith BA, Thorpe K, Wrong Z, Royle NJ, Jeffrey AJ, Ponder BAJ (1987) Deletion of genes on chromosome 1 in endocrine neoplasia. Nature 328:524–526

    Google Scholar 

  • Merlo GR, Siddiqui J, Cropp C, Liscia PS, Lidereau R, Callahan R, Kufe DW (1989) Frequent alteration of the DF3 tumor-associated antigen gene in primary human breast carcinomas. Cancer Res 49:6966–6971

    Google Scholar 

  • Montpezat JP, Delattre O, Bernard A, Grundwald D, Remvikos Y, Muleris M, Salmon RJ, Frelat G, Dutrillaux B, Thomas G (1988) Loss of alleles on chromosome 18 and on the short arm of chromosome 17 in polyploid colorectal carcinomas. Int J Cancer 41:404–408

    Google Scholar 

  • Morton NE, Bruns GA (1987) Report of the committee on the genetic constitution of chromosomes 1 and 2. (9th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 46:102–130

    Google Scholar 

  • Nau MM, Brooks BJ, Battey J, Sausville E, Gazdar AF, Kirsch IR, McBride OW, Bertness V, Hollis GF, Minna JD (1985) L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature 318:69–73

    Google Scholar 

  • Naylor SL, Johnson BE, Minna JD, Sakaguchi AY (1987) Loss of heterozygosity of chromosome 3p markers in small-cell lung cancer. Nature 329:451–454

    Google Scholar 

  • Okamoto M, Sasaki M, Sugio K, Sato C, Ivana T, Ikeuchi T, Tonomura A, Sasasuki T, Miyaki M (1988) Loss of constitutional heterozygosity in colon carcinoma from patients with familial polyposis coli. Nature 331:273–277

    Google Scholar 

  • Paraskeva C, Harvey A, Finerty S, Powell S (1989) Possible involvement of chromosome 1 in in vitro immortalization: evidence from progression of a human adenoma-derived cell line in vitro. Int J Cancer 43:743–746

    Google Scholar 

  • Pathak S, Goodacre A (1986) Specific chromosome anomalies and predisposition to human breast, renal cell, and colorectal carcinoma. Cancer Genet Cytogenet 19:29–36

    Google Scholar 

  • Rushdi A, Nishikura K, Erickson J, Watt R, Rovera G, Croce CM (1983) Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma. Science 222:390–393

    Google Scholar 

  • Seemayer TA, Cavenee WE (1989) Biology of disease: molecular mechanisms of oncogenesis. Lab Invest 60:585–599

    Google Scholar 

  • Solomon E, Voss R, Hall V, Bodmer WF, Jass JR, Jeffreys AJ, Lucibello FC, Patel I, Rider SH (1987) Chromosome 5 allele loss in human colorectal carcinomas. Nature 328:616–619

    Google Scholar 

  • Stoler A, Bouck N (1985) Identification of a single chromosome in the normal human genome essential for suppression of hamster cell transformation. Proc Natl Acad Sci USA 82:570–574

    Google Scholar 

  • Swallow D, Gendler S, Griffiths B, Kearney A, Povey S, Sheer D, Palmer RW, Taylor-Papadimitriou J (1987) The human tumor associated epithelial mucins are coded by an expressed hypervariable gene locus. Am Hum Genet 51:289–294

    Google Scholar 

  • T'Ang A, Varley JM, Chakraborty S, Linn-Murphee A, Fung YKT (1988) Structural rearrangement of the retinoblastoma gene in human breast carcinoma. Science 242:263–266

    Google Scholar 

  • Theillet C, Lidereau R, Escot C, Hutzelt P, Brunet M, Gest J, Schlom J, Callahan R (1986) Loss of a c-Ha-ras-1 allele and aggressive human primary breast carcinomas. Cancer Res 46:4776–4781

    Google Scholar 

  • Trent JM (1985) Cytogenetic and molecular biologic alterations in human breast cancer: a review. Breast Cancer Res Treat 5:221–229

    Google Scholar 

  • Tsutsumi M, Yokota J, Kakizoe T, Koiso K, Sugimura T, Terada M (1989) Loss of heterozygosity on chromosomes 1p and 11p in sporadic pheochromocytoma. J Natl Cancer Inst 81:367–370

    Google Scholar 

  • Varley JM, Armour J, Swallow JE, Jeffreys AJ, Ponder BAJ, T'Ang A, Fung YKT, Brammar WJ, Walker RA (1989) The retinoblastoma gene is frequently altered leading to loss of expression in primary breast tumors. Oncogene 4:725–729

    Google Scholar 

  • Vogelstein B, Fesrou ER, Hamilton SR, Kern SE, Presinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos SL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532

    Google Scholar 

  • Weinberg RA (1989) Oncogenesis, anti-oncogenesis and the molecular bases of multistep carcinogenesis. Cancer Res 49:3713–3721

    Google Scholar 

  • Yokota J, Wada M, Shimosato Y, Terada M, Sugimura T (1987) Loss of heterozygosity on chromosome 3, 13 and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung. Proc Natl Acad Sci USA 84:9252–9256

    Google Scholar 

  • Yokota J, Wada M, Yoshida T, Noguchi M, Terasaki T, Shimosato Y, Sugimura T, Terada M (1988) Heterogeneity of lung cancer cells with respect to the amplification and rearrangement of myc family oncogenes. Oncogene 2:607–611

    Google Scholar 

  • Zbar B, Brauch H, Talmadge C, Linehan M (1987) Loss of alleles of loci on the short arm of chromosome 3 in renal cell carcinoma. Nature 327:721–724

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre René Huguenin, 5, Rue Gaston Latouche, F-92211, St. Cloud, France

    Ivan Bieche, Marie-Helene Champeme & Rosette Lidereau

  2. Laboratory of Tumor Immunology and Biology, NCI, National Institute of Health, 20892, Bethesda, MD, USA

    Giorgio Merlo & Robert Callahan

  3. Unité INSERM 301, IGM, 27, Rue Charlotte Dodu, F-75011, Paris, France

    Christian-Jacques Larsen

Authors
  1. Ivan Bieche
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marie-Helene Champeme
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giorgio Merlo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christian-Jacques Larsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert Callahan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rosette Lidereau
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bieche, I., Champeme, MH., Merlo, G. et al. Loss of heterozygosity of the L-myc oncogene in human breast tumors. Hum Genet 85, 101–105 (1990). https://doi.org/10.1007/BF00276332

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00276332

Keywords

Search

Navigation