Cancer Cytogenetics: An Introduction

  • Thomas S. K. WanEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1541)


The Philadelphia chromosome was the first chromosomal abnormality discovered in cancer using the cytogenetics technique in 1960, and was consistently associated with chronic myeloid leukemia. Over the past five decades, innovative technical advances in the field of cancer cytogenetics have greatly enhanced the detection ability of chromosomal alterations, and have facilitated the research and diagnostic potential of chromosomal studies in neoplasms. These developments notwithstanding, chromosome analysis of a single cell is still the easiest way to delineate and understand the relationship between clonal evolution and disease progression of cancer cells. The use of advanced fluorescence in situ hybridization (FISH) techniques allows for the further identification of chromosomal alterations that are unresolved by the karyotyping method. It overcame many of the drawbacks of assessing the genetic alterations in cancer cells by karyotyping. Subsequently, the development of DNA microarray technologies provides a high-resolution view of the whole genome, which may add massive amounts of new information and opens the field of cancer cytogenomics. Strikingly, cancer cytogenetics does not only provide key information to improve the care of patients with malignancies, but also acts as a guide to identify the genes responsible for the development of these neoplastic states and has led to the emergence of molecularly targeted therapies in the field of personalized medicine.

Key words

Cancer cytogenetics FISH Karyotyping Molecular cytogenetics Review 



The author thanks Eden Wan for drawing Figs. 1 and 2.


  1. 1.
    Tjio JH, Levan A (1956) The chromosome number in man. Hereditas 42:1–6CrossRefGoogle Scholar
  2. 2.
    Nowell PC, Hungerford DA (1960) A minute chromosome in human chronic granulocytic leukemia. Science 132:1497Google Scholar
  3. 3.
    Rowley JD (1973) A new consistent chromosomal abnormality in chronic myelogeneous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243:290–293CrossRefPubMedGoogle Scholar
  4. 4.
    Konopka JB, Watanabe SM, Singer JW et al (1985) Cell lines and clinical isolates derived from Ph’-positive chronic myelogeneous leukemia patients express c-abl proteins with a common structural alteration. Proc Natl Acad Sci U S A 82:1810–1814CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Vardiman JW, Thiele J, Arber DA et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasm and acute leukemia: rationale and important changes. Blood 114:937–951CrossRefPubMedGoogle Scholar
  6. 6.
    Manuelidis L, Langer-Safer PR, Ward DC (1982) High-resolution mapping of satellite DNA using biotin-labeled DNA probes. J Cell Biol 95:619–625CrossRefPubMedGoogle Scholar
  7. 7.
    Wan TS, Ma ES (2012) Molecular cytogenetics: an indispensable tool for cancer diagnosis. Chang Gung Med J 35:96–110PubMedGoogle Scholar
  8. 8.
    Wan TS, Ma ES (2012) The role of FISH in hematologic cancer. Int J Hematol Oncol 1:71–86CrossRefGoogle Scholar
  9. 9.
    Wan TS (2014) Cancer cytogenetics: methodology revisited. Ann Lab Med 34:413–425CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Yunis JJ (1982) Comparative analysis of high-resolution chromosome techniques for leukemic bone marrows. Cancer Genet Cytogenet 7:43–50CrossRefPubMedGoogle Scholar
  11. 11.
    Garipidou V, Secker-Walker LM (1991) The use of fluorodeoxyuridine synchronization for cytogenetic investigation of acute lymphoblastic leukemia. Cancer Genet Cytogenet 52:107–111CrossRefPubMedGoogle Scholar
  12. 12.
    Saxe DF, Persons DL, Wolff DJ, Cytogenetics Resource Committee of the College of American Pathologists et al (2012) Validation of fluorescence in situ hybridization using an analyste-specific reagent for detection of abnormalities involving the mixed lineage leukemia gene. Arch Pathol Lab Med 136:47–52CrossRefPubMedGoogle Scholar
  13. 13.
    Kallioniemi A, Kallioniemi OP, Sudar D et al (1992) Compararive genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258:818–821CrossRefPubMedGoogle Scholar
  14. 14.
    Pinkel D, Segraves R, Sudar D et al (1998) High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 20:207–211CrossRefPubMedGoogle Scholar
  15. 15.
    Schröck E, du Manoir S, Veldman T et al (1996) Multicolor spectral karyotyping of human chromosomes. Science 273:494–497CrossRefPubMedGoogle Scholar
  16. 16.
    Speicher MR, Gwyn Ballard S, Ward DC (1996) Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nat Genet 12:368–375CrossRefPubMedGoogle Scholar
  17. 17.
    Chudoba I, Plesch A, Lörch T et al (1999) High resolution multicolor-banding: a new technique for refine FISH analysis of human chromosomes. Cytogenet Cell Genet 84:156–160CrossRefPubMedGoogle Scholar
  18. 18.
    Tsao SW, Wong N, Wang X et al (2001) Nonrandom chromosomal imbalances in human ovarian surface epithelial cells immortalized by HPV16-E6E7 viral oncogenes. Cancer Genet Cytogenet 130:141–149CrossRefPubMedGoogle Scholar
  19. 19.
    Hu YC, Lam KY, Law SY et al (2002) Establishment, characterization, karyotyping, and comparative genomic hybridization analysis of HKESC-2 and HKESC-3, two newly established human esophageal squamous cell carcinoma cell lines. Cancer Genet Cytogenet 135:120–127CrossRefPubMedGoogle Scholar
  20. 20.
    Wong MP, Fung LF, Wang E et al (2003) Chromosomal aberrations of primary lung adenocarcinomas in nonsmokers. Cancer 97:1263–1270CrossRefPubMedGoogle Scholar
  21. 21.
    Wan TS, Martens UM, Poon SS et al (1999) Absence or low number of telomere repeats at junctions of dicentric chromosomes. Genes Chromosomes Cancer 24:83–86CrossRefPubMedGoogle Scholar
  22. 22.
    Mitelman F, Johansson B, Mertens F (eds) Mitelman database of chromosome aberrations in cancer. (Updated on May 4, 2016)
  23. 23.
    Atlas of genetics and cytogenetics in oncology and haematology.
  24. 24.
    Shaffer LG, Tommerup N (eds) (2005) ISCN (2005): an international system for human cytogenetic nomenclature. S. Karger, BaselGoogle Scholar
  25. 25.
    McGowan-Jordan J, Simons A, Schmid M (eds) (2016) An international system for human cytogenomic nomenclature. S. Karger, Basel. [Reprint of Cytogenet Genome Res 149(1–2)]Google Scholar
  26. 26.
    Mitelman F, Rowley JD (2007) ISCN (2005) is not acceptable for describing clonal evolution in cancer. Genes Chromosomes Cancer 46:213–214CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Haematology Division, Department of Anatomical & Cellular PathologyThe Chinese University of Hong Kong, Prince of Wales HospitalShatinHong Kong

Personalised recommendations