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Conventional and Molecular Cytogenetics in Cancer

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Book cover Molecular Testing in Cancer

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Abstract

The discovery of the Philadelphia chromosome in 1960, its subsequent characterization as a 9;22 translocation in 1973, and the cloning of the BCR and ABL1 genes that fuse as a result of the translocation opened the field of genomic medicine. The techniques of chromosomal analysis by G-banding and fluorescence in situ hybridization (FISH) that enabled researchers to make these discoveries are still commonly used today and remain invaluable means to diagnose and monitor many different constitutional and acquired diseases. Conventional cytogenetic analysis by G-banding permits the identification of numerical (gain or loss of a chromosome) and/or structural (translocation, deletion, inversion, etc.) abnormalities present in metaphase (dividing) cells. FISH can detect numerical abnormalities and characteristic gene fusions or rearrangements in interphase (nondividing) cells and additionally can detect abnormalities that may be cryptic (undetectable by G-banding). Whereas G-banding analysis provides a whole-genome view, FISH provides targeted analysis of only those genes or loci to which the probe is complementary. Each, however, has its place and can be used strategically to permit accurate diagnosis and therapeutic monitoring for minimal residual disease. In light of the rapid advances being made in genomic technologies such as array-based comparative genomic hybridization and next-generation sequencing, it is critical for clinicians and laboratorians to work together to determine the best testing algorithms for individual patients.

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References

  1. Tjio JH, Levan A. The chromosome number of man. Hereditas. 1956;42:1–6.

    Article  Google Scholar 

  2. Ford CE, Hamerton JL. The chromosomes of man. Nature. 1956;178:1020–3.

    Article  CAS  PubMed  Google Scholar 

  3. Gersen SL, Keagle MB, editors. The principles of clinical cytogenetics. 3rd ed. New York: Springer Science + Business Media; 2013.

    Google Scholar 

  4. Harper PS. First years of human chromosomes. Bloxham: Scion Publishing Ltd; 2006.

    Google Scholar 

  5. Smeets DF. Historical prospective of human cytogenetics: from microscope to microarray. Clin Biochem. 2004;37:439–46.

    Article  CAS  PubMed  Google Scholar 

  6. Sumner AT. Chromosome banding. London: Unwin Hyman; 1990.

    Google Scholar 

  7. Trask BJ. Human cytogenetics: 46 chromosomes, 46 years and counting. Nat Rev Genet. 2002;3:769–78.

    Article  CAS  PubMed  Google Scholar 

  8. Nowell PC, Hungerford DA. A minute chromosome in human chronic granulocytic leukemia. Science. 1960;132:1497.

    Google Scholar 

  9. Chandra HS, Heisterkamp NC, Hungerford A, Morrissette JJ, Nowell PC, Rowley JD, et al. Philadelphia Chromosome Symposium: commemoration of the 50th anniversary of the discovery of the Ph chromosome. Cancer Genet. 2011;204:171–9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Rowley JD. A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973;243:290–3.

    Article  CAS  PubMed  Google Scholar 

  11. de Klein A, van Kessel AG, Grosveld G, Bartram CR, Hagemeijer A, Bootsma D, et al. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature. 1982;300:765–7.

    Article  PubMed  Google Scholar 

  12. Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G. Philadelphia chromosomal breakpoints are clustered with a limited region, bcr, on chromosome 22. Cell. 1984;36:93–9.

    Article  CAS  PubMed  Google Scholar 

  13. Heisterkamp N, Stephenson JR, Groffen J, Hansen PF, de Klein A, Bartram CR, et al. Localization of the c-abl oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature. 1983;306:239–42.

    Article  CAS  PubMed  Google Scholar 

  14. Heisterkamp N, Stam K, Groffen J, de Klein A, Grosveld G. Structural organization of the bcr gene and its role in the Ph’ translocation. Nature. 1985;315:758–61.

    Article  CAS  PubMed  Google Scholar 

  15. Mitelman F, Johansson B, Mertens F, editors. Mitelman database of chromosome aberrations and gene fusions in cancer. 2013. http://cgap.nci.nih.gov/Chromosomes/Mitelman

  16. Barch MJ, Knutsen T, Spurbeck JL, editors. The AGT cytogenetics laboratory manual. 3rd ed. Philadelphia: Lippincott-Raven; 1997.

    Google Scholar 

  17. Swansbury J, editor. Cancer cytogenetics—methods and protocols. Totowa: Humana Press; 2003.

    Google Scholar 

  18. Wegner R-D, editor. Diagnostic cytogenetics. Berlin: Springer; 1999.

    Google Scholar 

  19. Heerema NA, Byrd JC, Cin PSD, Dell’ Aquila ML, Koduru PRK, Aviram A, et al. Stimulation of chronic lymphocytic leukemia cells with CpG oligodeoxynucleotide gives consistent karyotypic results among laboratories: a CLL Research Consortium (CRC) Study. Cancer Genet Cytogenet. 2010;203:134–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dicker F, Schnittger S, Haferlach T, Kern W, Schoch C. Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: a study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression. Blood. 2006;108:3152–60.

    Article  CAS  PubMed  Google Scholar 

  21. Shaffer LG, McGowan-Jordan J, Schmid M, editors. ISCN (2013): an international system for human cytogenetic nomenclature. Basel: S. Karger; 2013.

    Google Scholar 

  22. Mascarello JT, Hirsch B, Kearney HM, Ketterling RP, Olson SB, Quigley DI, et al. Section E9 of the American College of Medical Genetics technical standards and guidelines: fluorescence in situ hybridization. Genet Med. 2011;13:667–75.

    Article  PubMed  Google Scholar 

  23. Wolff DJ, Bagg A, Cooley LD, Dewald GW, Hirsch BA, Jacky PB, et al. Guidance for fluorescence in situ hybridization testing in hematologic disorders. J Mol Diagn. 2007;9:134–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wiktor AE, van Dyke DL, Stupca PJ, Ketterling RP, Thorland EC, Shearer BM, et al. Preclinical validation of fluorescence in situ hybridization assays for clinical practice. Genet Med. 2006;8:16–23.

    Article  CAS  PubMed  Google Scholar 

  25. Liehr T, editor. Fluorescence in situ hybridization (FISH). Berlin: Springer; 2009.

    Google Scholar 

  26. Bridger JM, Volpi EV, editors. Fluorescence in situ hybridization (FISH)—protocols and applications. New York: Springer Science + Business Media; 2010.

    Google Scholar 

  27. Al-Mulla F, editor. Formalin-fixed paraffin-embedded tissues—methods and protocols. New York: Springer Science + Business Media; 2011.

    Google Scholar 

  28. Ambros PF, Ambros IM, Brodeur GM, Haber M, Khan J, Nakagawara A, et al. International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee. Br J Cancer. 2009;100:1471–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cohn SL, Pearson ADJ, London WB, Monclair T, Ambros PF, Brodeur GM, et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG task force report. J Clin Oncol. 2009;27:289–97.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Schneiderman J, London WB, Brodeur GM, Castleberry RP, Look AT, Cohn SL. Clinical significance of MYCN amplification and ploidy in favorable-stage neuroblastoma: a report from the Children’s Oncology Group. J Clin Oncol. 2008;26:913–8.

    Article  PubMed  Google Scholar 

  31. Mueller S, Matthay KK. Neuroblastoma: biology and staging. Curr Oncol Rep. 2009;11:431–8.

    Article  PubMed  Google Scholar 

  32. Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist. 2009;14:320–68.

    Article  CAS  PubMed  Google Scholar 

  33. Wolff AC, Hammond MEH, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. 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. 2006;25:118–45.

    Article  PubMed  Google Scholar 

  34. Wolff AC, Hammond MEH, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer. American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med. doi:10.5858/arpa.2013-0953-SA.

  35. Bang Y-J, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positiveadvanced gastric or gastro-oesophageal junction cancer(ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.

    Article  CAS  PubMed  Google Scholar 

  36. Yoon HH, Shi Q, Sukov WR, Wiktor AE, Khan M, Sattler CA, et al. Association of HER2/ErbB2 expression and gene amplification with pathologic features and prognosis in esophageal adenocarcinomas. Clin Cancer Res. 2012;18:546–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Vance GH, Barry TS, Bloom KJ, Fitzgibbons PL, Hicks DG, Jenkins RB, et al. Genetic heterogeneity in HER2 testing. Arch Pathol Lab Med. 2009;133:611–2.

    PubMed  Google Scholar 

  38. Laudadio J, Quigley DI, Tubbs R, Wolff DJ. HER2 testing: a review of detection methodologies and their clinical performance. Expert Rev Mol Diagn. 2007;7:53–62.

    Article  CAS  PubMed  Google Scholar 

  39. Gruver AM, Peerwani Z, Tubbs RR. Out of the darkness and into the light: bright field in situ hybridisation for delineation of ERBB2 (HER2) status in breast carcinoma. J Clin Pathol. 2010;63:210–9.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Mansfield AS, Sukov WR, Eckel-Passow JE, Sakai Y, Walsh FJ, Lonzo M, et al. Comparison of fluorescence in situ hybridization (FISH) and dual-ISH (DISH) in the determination of HER2 status in breast cancer. Am J Clin Pathol. 2013;139:144–50.

    Article  PubMed  Google Scholar 

  41. Sokolova IA, Halling KC, Jenkins RB, Burkhardt HM, Meyer RG, Seelig SA, et al. The development of a multitarget, multicolor fluorescence in situ hybridization assay for the detection of urothelial carcinoma in urine. J Mol Diagn. 2010;2:116–23.

    Article  Google Scholar 

  42. Halling KC, Kipp BR. Fluorescence in situ hybridization in diagnostic cytology. Hum Pathol. 2007;38:1137–44.

    Article  CAS  PubMed  Google Scholar 

  43. Haferlach C, Dicker F, Schnittger S, Kern W, Haferlach T. Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgVH status and immunophenotyping. Leukemia. 2007;21:2442–51.

    Article  CAS  PubMed  Google Scholar 

  44. Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Arch Pathol Lab Med. 2013;137:828–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yi ES, Chung J-H, Kulig K, Kerr KM. Detection of anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer and related issues in ALK inhibitor therapy. Mol Diagn Ther. 2012;16:143–50.

    Article  CAS  PubMed  Google Scholar 

  46. Camidge DR, Theodoro M, Maxson DA, Skokan M, O’Brien T, Lu X, et al. Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization-positive nonsmall cell lung cancer. Cancer. 2012;118:4486–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gerber DE, Minna JD. ALK inhibition for non-small cell lung cancer: from discovery to therapy in record time. Cancer Cell. 2010;18:548–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Minnesota, MMC 609, 420 Delaware St. SE, Minneapolis, MN, 55455, USA

    Michelle Dolan M.D.

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  1. Michelle Dolan M.D.
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Correspondence to Michelle Dolan M.D. .

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Editors and Affiliations

  1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    George M. Yousef

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Serge Jothy

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Dolan, M. (2014). Conventional and Molecular Cytogenetics in Cancer. In: Yousef, G., Jothy, S. (eds) Molecular Testing in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-8050-2_2

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  • DOI: https://doi.org/10.1007/978-1-4899-8050-2_2

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4899-8049-6

  • Online ISBN: 978-1-4899-8050-2

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