Skip to main content

Advertisement

SpringerLink
Log in

Molecular cytogenetics in translational oncology: when chromosomes meet genomics

  • Educational Series
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

The discovery of the genetic changes that contribute to cellular neoplastic transformation is one of the major aims in oncological research. Chromosome rearrangements account for a large part of these initiating mutations that, resulting in gene deregulation, are the main target of molecular cytogenetics. Cytogenetics, based in reasoned genomic and biological questions and supported by the development of new biotechnological tools, is a powerful discipline that is continuously generating pieces of information that have immediate translation as reagents for diagnosis and useful research data. The present review presents a summary of the major cytogenetic findings that already have a clear role in clinical oncology because of their use as diagnostic markers, as indicators of molecular therapy suitability or both. We also present an updated description of the molecular cytogenetics tools that have included genomic advances in their most recent releases: multicolour fluorescence in situ hybridisation methods (e.g. SKY karyotyping) and array-based comparative genomic hybridisation (arrayCGH).

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

  1. Mitelman F, Johansson B, Mertens F (2007) The impact of translocations and gene fusions on cancer causation. Nat Rev Cancer 7:233–245

    Article  PubMed  CAS  Google Scholar 

  2. Tjio JH, Levan A (1956) The chromosome number of men. Hereditas 42:1–6

    Article  Google Scholar 

  3. Nowell PC, Hungerford DA (1960) A minute chromosome in human chronic granulocytic leukemia. Science 132:1497

    Google Scholar 

  4. Mitelman F, Johansson B, Mertens F (2007) Mitelman Database of Chromosome Aberrations in Cancer [online]. http://cgap.nci.nih.gov/Chromosomes/Mitelman

  5. Kearney L, Horsley SW (2005) Molecular cytogenetics in haematological malignancy: current technology and future prospects. Chromosoma 114:286–294

    Article  PubMed  CAS  Google Scholar 

  6. Speicher MR, Carter NO (2005) The new cytogenetics: blurring the boundaries with molecular biology. Nat Rev Genet 6:782–792

    Article  PubMed  CAS  Google Scholar 

  7. Futreal PA, Coin L, Marshall M et al (2004) A census of human cancer genes. Nat Rev Cancer 4:177–183

    Article  PubMed  CAS  Google Scholar 

  8. Sjöblom T, Jones S, Wood LD et al (2006) The consensus coding sequences of human breast and colorectal cancers. Science 314:268–274

    Article  PubMed  CAS  Google Scholar 

  9. Rowley JD (2001) Chromosome translocations: dangerous liaisons revisited. Nat Rev Cancer 1: 245–250

    Article  PubMed  CAS  Google Scholar 

  10. Tomlins SA, Laxman B, Dhanasekaran SM et al (2007) Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature 448:595–599

    Article  PubMed  CAS  Google Scholar 

  11. Tomlins SA, Rhodes DR, Perner S et al (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310:644–648

    Article  PubMed  CAS  Google Scholar 

  12. Mitelman F, Johansson B, Mertens F (2004) Fusion genes and rearranged genes as a linear function of chromosome aberrations in cancer. Nat Genet 36:331–334

    Article  PubMed  CAS  Google Scholar 

  13. Vanden Bempt I, Drijkoningen M, De Wolf-Peeters C (2007) The complexity of genotypic alterations underlying HER2-positive breast cancer: an explanation for its clinical heterogeneity. Curr Opin Oncol 19:552–557

    Google Scholar 

  14. Johnson PH, Esteva FJ (2007) The use of HER2 modulation in the adjuvant setting. Curr Oncol Rep 9:9–16

    Article  PubMed  CAS  Google Scholar 

  15. Wolff AC, Hammond ME, Schwartz JN et al (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145

    Article  PubMed  CAS  Google Scholar 

  16. Engelman JA, Cantley LC (2006) The role of the ErbB family members in non-small cell lung cancers sensitive to epidermal growth factor receptor kinase inhibitors. Clin Cancer Res 12:4372s–4376s

    Article  PubMed  CAS  Google Scholar 

  17. Swanton C, Futreal A, Eisen T (2006) Targeted therapies in non-small cell lung cancer. Clin Cancer Res 12:4377s–4383s

    Article  PubMed  CAS  Google Scholar 

  18. Martinez-Ramirez A, Urioste M, Contra T et al (2001) Fluorescence in situ hybridization study of TEL/AML1 fusion and other abnormalities involving TEL and AML1 genes. Correlation with cytogenetic findings and prognostic value in children with acute lymphocytic leukemia. Haematologica 86:1245–1253

    PubMed  CAS  Google Scholar 

  19. Martinez-Ramirez A, Cigudosa JC, Maestre L et al (2004) Simultaneous detection of the immunophenotypic markers and genetic aberrations on routinely processed paraffin sections of lymphoma samples by means of the FICTION technique. Leukemia 18:348–353

    Article  PubMed  CAS  Google Scholar 

  20. Saez B, Martin-Subero JI, Odero MD et al (2007) Multicolor interphase cytogenetics for the study of plasma cell dyscrasias. Oncol Rep 18:1099–1106

    PubMed  CAS  Google Scholar 

  21. Sherbenou DW, Druker BJ (2007) Applying the discovery of the Philadelphia chromosome. J Clin Invest 117:2067–2074

    Article  PubMed  CAS  Google Scholar 

  22. Veldman T, Vignon C, Schrock E et al (1997) Hidden chromosome abnormalities in haematological malignancies detected by multicolour spectral karyotyping. Nat Genet 15:406–410

    Article  PubMed  CAS  Google Scholar 

  23. Cigudosa JC, Calasanz MJ, Garcia Miranda JL (1999) Multicolor spectral karyotyping (SKY) and its application to the cytogenetic diagnosis of multiple myeloma. Sangre (Barc) 44:301–304

    CAS  Google Scholar 

  24. Cigudosa JC, Odero MD, Calasanz MJ et al (2003) De novo erythroleukemia chromosome features include multiple rearrangements, with special involvement of chromosomes 11 and 19. Genes Chromosomes Cancer 36:406–412

    Article  PubMed  CAS  Google Scholar 

  25. Martinez-Ramirez A, Rodriguez Perales S, Melendez B et al (2003) Characterization of the A673 cell line (Ewing tumor) by molecular cytogenetic techniques. Cancer Genet Cytogenet 141: 138–142

    Article  PubMed  CAS  Google Scholar 

  26. Rao PH, Cigudosa JC, Ning Y et al (1998) Multicolor spectral karyotyping identifies new recurring breakpoints and translocations in multiple myeloma. Blood 92:1743–1748

    PubMed  CAS  Google Scholar 

  27. Rodriguez-Perales S, Martinez-Ramirez A, de Andres SA et al (2004) Molecular cytogenetic characterization of rhabdomyosarcoma cell lines. Cancer Genet Cytogenet 148:35–43

    Article  PubMed  CAS  Google Scholar 

  28. Saez B, Martin-Subero JI, Largo C et al (2006) Identification of recurrent chromosomal breakpoints in multiple myeloma with complex karyotypes by combined G-banding, spectral karyotyping, and fluorescence in situ hybridization analyses. Cancer Genet Cytogenet 169:143–149

    Article  PubMed  CAS  Google Scholar 

  29. Kallioniemi A, Kallioniemi OP, Sudar D et al (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258:818–821

    Article  PubMed  CAS  Google Scholar 

  30. Gebhart E, Verdorfer I, Saul W et al (2000) Delimiting the use of comparative genomic hybridization in human myeloid neoplastic disorders. Int J Oncol 16:1099–1105

    PubMed  CAS  Google Scholar 

  31. Gebhart, E (2005) Genomic imbalances in human leukemia and lymphoma detected by comparative genomic hybridization (Review). Int J Oncol 27: 593–606

    PubMed  CAS  Google Scholar 

  32. Lucito R, West J, Reiner A et al (2000) Detecting gene copy number fluctuations in tumor cells by microarray analysis of genomic representations. Genome Res 10:1726–1736

    Article  PubMed  CAS  Google Scholar 

  33. Mei R, Galipeau PC, Prass C et al (2000) Genome-wide detection of allelic imbalance using human SNPs and high-density DNA arrays. Genome Res 10:1126–1137

    Article  PubMed  CAS  Google Scholar 

  34. Pollack JR, Perou CM, Alizadeh AA et al (1999) Genome-wide analysis of DNA copy-number changes using cDNA microarrays. Nat Genet 23:41–46

    Article  PubMed  CAS  Google Scholar 

  35. Solinas-Toldo S, Lampel S, Stilgenbauer S et al (1997) Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosomes Cancer 20:399–407

    Article  PubMed  CAS  Google Scholar 

  36. Fiegler H, Carr P, Douglas EJ et al (2003) DNA microarrays for comparative genomic hybridization based on DOP-PCR amplification of BAC and PAC clones. Genes Chromosomes Cancer 36: 361–374

    Article  PubMed  CAS  Google Scholar 

  37. Ishkanian AS, Malloff CA, Watson SK et al (2004) A tiling resolution DNA microarray with complete coverage of the human genome. Nat Genet 36:299–303

    Article  PubMed  CAS  Google Scholar 

  38. Paulsson K, Heidenblad M, Strömbeck B et al (2006) High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration. Leukemia 20:840–846

    Article  PubMed  CAS  Google Scholar 

  39. Rücker FG, Bullinger L, Schwaenen C et al (2006) Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization. J Clin Oncol 24:3887–3894

    Article  PubMed  CAS  Google Scholar 

  40. Rücker FG, Sander S, Döhner K et al (2006) Molecular profiling reveals myeloid leukemia cell lines to be faithful model systems characterized by distinct genomic aberrations. Leukemia 20:994–1001

    Article  PubMed  CAS  Google Scholar 

  41. Martinez-Ramirez A, Urioste M, Melchor L et al (2005) Analysis of myelodysplastic syndromes with complex karyotypes by high-resolution comparative genomic hybridization and subtelomeric CGH array. Genes Chromosomes Cancer 42:287–298

    Article  PubMed  CAS  Google Scholar 

  42. Alvarez S, Cigudosa JC (2005) Gains, losses and complex karyotypes in myeloid disorders: a light at the end of the tunnel. Hematol Oncol 23:18–25

    Article  PubMed  Google Scholar 

  43. Suela J, Largo C, Ferreira B et al (2007) Neurofibromatosis 1, and Not TP53, seems to be the main target of chromosome 17 deletions in de novo acute myeloid leukemia. J Clin Oncol 25:1151–1152

    Article  PubMed  Google Scholar 

  44. Suela J, Alvarez S, Cifuentes F et al (2007) DNA profiling analysis of 100 consecutive de novo acute myeloid leukemia cases reveals patterns of genomic instability that affect all cytogenetic risk groups. Leukemia 21:1224–1231

    Article  PubMed  CAS  Google Scholar 

  45. Gorletta TA, Gasparini P, D’Elios MM et al (2005) Frequent loss of heterozygosity without loss of genetic material in acute myeloid leukemia with a normal karyotype. Genes Chromosomes Cancer 44:334–337

    Article  PubMed  CAS  Google Scholar 

  46. Raghavan M, Lillington DM, Skoulakis S et al (2005) Genome-wide single nucleotide polymorphism analysis reveals frequent partial uniparental disomy due to somatic recombination in acute myeloid leukemias. Cancer Res 65:375–378

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Genetics, University of Navarra, Pamplona, Spain

    M. José Calasanz

  2. Molecular Cytogenetics Group, CIBER on Rare Diseases (CIBERER), Madrid, Spain

    Juan C. Cigudosa

  3. Molecular Cytogenetics Group, Centro Nacional de Investigaciones Oncológicas (CNIO), C/ Melchor Fernández Almagro 3, 28029, Madrid, Spain

    Juan C. Cigudosa

Authors
  1. M. José Calasanz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juan C. Cigudosa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juan C. Cigudosa.

Additional information

Supported by an unrestricted educational grant from Roche Farma S.A.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Calasanz, M.J., Cigudosa, J.C. Molecular cytogenetics in translational oncology: when chromosomes meet genomics. Clin Transl Oncol 10, 20–29 (2008). https://doi.org/10.1007/s12094-008-0149-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-008-0149-1

Keywords

Search

Navigation