Skip to main content
SpringerLink
Log in

The Molecular Oncology of 12q13–15

  • Conference paper
Chromosome 12 Aberrations in Human Solid Tumors

  • 39 Accesses

Abstract

Since the observation of alterations in the same cytogenetical breakpoint region 12q13–15 in a group of solid human tumors, the relationship between the breakpoints and the chromosomal localization of oncogenes or suppressor genes has been of particular interest. In this region, four oncogenes (sas, mdm-2, wnt-1, gli) and two putative suppressor genes (rap1B, CHOP) have been localized (Fig. 1). The main results obtained concerning the function of these genes during normal development and their implications for tumorigenesis will be discussed in this chapter.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aman P, Ron D, Mandahl N, Fioretos T, Heim S, Arheden K, Willén H, Rydholm A, Mitelman F (1992) Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11). Genes Chrom Cancer 5:278–286

    Article  PubMed  CAS  Google Scholar 

  • Arheden K, Tommerup N, Mandahl N, Heim S, Winther J, Jensen OA, Prause JU, Mitelman F (1988a) Amplification of the human putative oncogene int1 in primary retinoblastoma tumors. Cytogenet Cell Genet 48:174–177

    Article  PubMed  CAS  Google Scholar 

  • Arheden K, Mandahl N, Strömbeck B, Isaksson M, Mitelman F (1988b) Chromosome localization of the human oncogene intl to 12q13 by in situ hybridization. Cytogenet Cell Genet 47:86–87

    Article  PubMed  CAS  Google Scholar 

  • Arheden K, Mandahl N, Heim S, Mitelman F (1989a) The intl oncogene is not rearranged or amplified in lipomas with structural chromosomal abnormalities of 12q13–15. Cancer Genet Cytogenet 42:143–146

    Article  PubMed  CAS  Google Scholar 

  • Arheden K, Nilbert M, Heim S, Mandahl N, Mitelman F (1989b) No amplification or rearrangement of INT1, GLI, or COL2A1 in uterine leiomyomas with t(12;14)(ql4–15; q23–24). Cancer Genet Cytogenet 39:195–201

    Article  PubMed  CAS  Google Scholar 

  • Arheden K, Ronne M, Mandahl N, Heim S, Kinzler KW, Vogelstein B, Mitelman F (1989c) In situ hybridization localizes the human putative oncogene gli to chromosome subbands 12q13.3–14.1. Hum Genet 82:1–2

    Article  PubMed  CAS  Google Scholar 

  • Cahilly-Snyder L, Yang-Feng T, Francke U, George DL (1987) Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Somat Cell Mol Genet 13:235–244

    Article  PubMed  CAS  Google Scholar 

  • Chen P-L, Chen Y, Bookstein R, Lee WH (1990) Genetic mechanisms of tumor suppression by the human p53 gene. Science 250:1576–1580

    Article  PubMed  CAS  Google Scholar 

  • Craig I, Gemmill R, Kucherlapati R, Craig S (1992) Report of the first international workshop on human chromosome 12 mapping. Cytogenet Cell Genet 61:243–262

    Article  PubMed  CAS  Google Scholar 

  • Crozat A, Aman P, Mandahl N, Ron D (1993) Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature 363:640–644

    Article  PubMed  CAS  Google Scholar 

  • Fakharzadeh SS, Trusko SP, George DL (1991) Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J 10:1565–1569

    PubMed  CAS  Google Scholar 

  • Fischer TH, Gatling MN, Lacal J-C, White GC (1990) Rap1B, a cAMP-dependent protein kinase substrate, associates with the platelet cytoskeleton. J Biol Chem 265:19405–19408

    PubMed  CAS  Google Scholar 

  • Fujii Y, Matui Y, Nakagawa Y, Hongo T, Igarashi Y, Yamada M, Nakagome Y, Tobayama S (1989) Translocation t(12;16)(q13;p11) in myxoid liposarcoma of a child and implication of the human int-1 gene in tumorigenesis. Jpn J Cancer Res 80:958–962

    Article  PubMed  CAS  Google Scholar 

  • Jakobovits A, Shackleford GM, Varmus HE, Martin GR (1986) Two proto-oncogenes implicated in mammary carcinogenesis, int-1 and int-2, are independently regulated during mouse development. Proc Natl Acad Sci USA 83:7806–7810

    Article  PubMed  CAS  Google Scholar 

  • Kinzler KW, Vogelstein B (1990) The gli gene encodes a nuclear protein which binds specific sequences in the human genome. Mol Cell Biol 10:634–642

    PubMed  CAS  Google Scholar 

  • Kinzler KW, Bigner SH, Bigner DD, Trent JM, Law ML, O’Brien SJ, Wong AJ, Vogelstein B (1987) Identification of an amplified, highly expressed gene in a human glioma. Science 236:70–73

    Article  PubMed  CAS  Google Scholar 

  • Molven A, Njolstad P, Fjose A (1991) Genomic structure and restricted neural expression of the zebrafish wnt-1 (int-1) gene. EMBO J 10:799–807

    PubMed  CAS  Google Scholar 

  • Momand J, Zambetti GP, Olson DC, George D, Levine AJ (1992) The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69:1237–1245

    Article  PubMed  CAS  Google Scholar 

  • Nusse R, Varmus HE (1982) Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31:99–109

    Article  PubMed  CAS  Google Scholar 

  • Nusse R, Varmus HE (1992) Wnt genes. Cell 69:1073–1987

    CAS  Google Scholar 

  • Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B (1992) Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358:80–86

    Article  PubMed  CAS  Google Scholar 

  • Paulien S, Turc-Carel C, Dal Cin P, Jani-Sait S, Sreekantaiah C, Leon GS, Vogelstein B, Kinzler KW, Sandberg AA, Gemmill RM (1990) Myxoid liposarcoma with t(12;16)(q13;p11) contains site specific alterations in methylation patterns surrounding a zinc-finger gene mapped to the breakpoint region on chromosome 12. Cancer Res 50:7902–7908

    PubMed  CAS  Google Scholar 

  • Pizon V, Chardin P, Lerosey I, Olofsson B, Tavitian A (1988a) Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the effector region. Oncogene 3:201–204

    PubMed  CAS  Google Scholar 

  • Pizon V, Lerosey I, Chardin P, Tavitian A (1988b) Nucleotide sequence of a human cDNA encoding a ras-related protein (raplB). Nucleic Acids Res 16:7719

    Article  PubMed  CAS  Google Scholar 

  • Rabbitts TH, Forster A, Larson R, Nathan P (1993) Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nature Genet 4:175–180

    Article  PubMed  CAS  Google Scholar 

  • Rijsewijk F, Schuermann M, Wagenaar E, Parren P, Weigel D, Nusse R (1987) The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell 50:649–657

    Article  PubMed  CAS  Google Scholar 

  • Roberts WM, Douglass EC, Peiper SC, Houghton PJ, Look AT (1989) Amplification of the gli gene in childhood sarcomas. Cancer Res 49:5407–5413

    PubMed  CAS  Google Scholar 

  • Rommel B (1991) Molekulargenetische Untersuchungen zum Einfluß bzw. zur Aktivierung von Proto-Onkogenen als Folge instabiler Chromatinkonfigurationen bei benignen Tumoren. Thesis, University of Bremen

    Google Scholar 

  • Ron D, Habiner JF (1992) CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant negative inhibitor of gene transcription. Genes Dev 6:439–453

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg UB, Schroder C, Preiss A, Kienfin A, Cote S, Riede I, Jackie H (1986) Structural homology of the product of the Drosophila Kruppel gene with Xenopus transcription factor IIIA. Nature 319:336–339

    Article  CAS  Google Scholar 

  • Rousseau-Merck MF, Pizon V, Tavitian A, Berger R (1990) Chromosome mapping of the human ras-related rap1A, rap1B, and rap2 genes to chromosomes lpl2–13, 12ql4, and 13q34, respectively. Cytogenet Cell Genet 52:2–4

    Article  Google Scholar 

  • Tsukamoto AS, Grosschedl R, Guzman RC, Parslow T, Varmus HE (1988) Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell 55:619–625

    Article  PubMed  CAS  Google Scholar 

  • Turc-Carel C, Dal Cin P, Limon J, Gibas Z, Kakati S, Pietrzak E, Parry D, Li F, Sandberg AA (1987a) Cytogenetic and molecular studies of adipose tissue tumors. Cancer Genet Cytogenet 28:33

    Article  Google Scholar 

  • Turc-Carel C, Pietrzak E, Kakati S, Kinniburgh AJ, Sandberg AA (1987b) The human int-1 gene is located at chromosome region 12ql2–12q13 and is not rearranged in myxoid liposarcoma with t(12;16)(q13;p11). Oncogene Res 1:397–405

    PubMed  CAS  Google Scholar 

  • Van’T Veer L, van Kessel AG, van Heerikhuizen H, van Ooyen A, Nusse R (1984) Molecular cloning and chromosomal assignment of the human homolog of int-1, a mouse gene implicated in mammary tumorigenesis. Mol Cell Biol 4:2532–2534

    Google Scholar 

  • Wong AJ, Bigner SH, Bigner DD, Kinzler KW, Hamilton SR, Vogelstein B (1987) Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci USA 84:6899–6903

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center of Human Genetics and Genetic Counselling, University of Bremen, Leobenerstr. ZHG, 28359, Bremen, Germany

    B. Rommel, J. Bullerdiek & W. Schloot

Authors
  1. B. Rommel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Bullerdiek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Schloot
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Zentrum f. Humangenetik u. Genetische Beratung, Universität Bremen, Leobener Straße, 28359, Bremen, Germany

    J. Bullerdiek  & S. Bartnitzke  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Rommel, B., Bullerdiek, J., Schloot, W. (1994). The Molecular Oncology of 12q13–15. In: Bullerdiek, J., Bartnitzke, S. (eds) Chromosome 12 Aberrations in Human Solid Tumors. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-06255-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-06255-5_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-06257-9

  • Online ISBN: 978-3-662-06255-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation