Molecular Cytogenetics in Medicine

An Overview
  • Yao-Shan Fan
Part of the Methods in Molecular Biology™ book series (MIMB, volume 204)


The word “chromosome” was introduced over a century ago from the Greek language meaning “colored body.” While cytogenetics refers to the study of chromosomes, the term molecular cytogenetics is used to describe the analysis of genomic alterations using mainly in situ hybridization based technology.


Comparative Genomic Hybridization Microdeletion Syndrome Maternal Serum Screening Peripheral Primitive Neuroectodermal Tumor Common Aneuploidy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Pinkel D., Straumer T., and Gray I. W. (1986) Cytogenetic analysis using quantitative, high-sensitivity, fluorescence in situ hybridization. Proc. Natl. Acad. Sci. USA 83, 2934–2938.PubMedCrossRefGoogle Scholar
  2. 2.
    Lawrence J. B., Villnave C. A., and Singer R. H. (1988) Sensitive, high-resolution chromatin and chromosome mapping in situ: presence and orientation of two closely integrated copies of EBV in a lymphoma line. Cell 52, 51–61.PubMedCrossRefGoogle Scholar
  3. 3.
    Fan Y. S., Davis L. M., and Shows T. B. (1990) Mapping small DNA sequences by fluorescence in situ hybridization directly on banded metaphase chromosomes. Proc. Natl. Acad. Sci. USA 87, 6223–6227.PubMedCrossRefGoogle Scholar
  4. 4.
    Lichter P., and Ward D. C. (1990) High resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science 247, 64–69.PubMedCrossRefGoogle Scholar
  5. 5.
    Pinkel D., Landegent C., Collins C., et al. (1988) Fluorescence in situ hybridization with human chromosome-specific libraries: detection of trisomy 21 and translocations of chromosome 4. Proc. Natl. Acad. Sci. USA 85, 9138–9142.PubMedCrossRefGoogle Scholar
  6. 6.
    Blennow E., Anneren G., Bui T-H., Berggren E., Asadi E., and Nordenskjold M. (1993) Characterization of supernumerary ring marker chromosomes by fluorescence in situ hybridization. Am. J. Hum. Genet. 53, 433–442.PubMedGoogle Scholar
  7. 7.
    Ledbetter D. H. and Ballabio A. (1995) Molecular cytogenetics of continuous gene syndromes: mechanisms and consequences of gene dosage imbalances, in The Metabolic and Molecular Bases of Inherited Diseases, 7th ed (Scriver C. R., Beaudet A., Sly W., and Valle D., eds.), McGraw Hill, New York, 811–839.Google Scholar
  8. 8.
    Klinger K., Landes G., Shook D., et al. (1992) Rapid detection of chromosome aneuploidies in uncultured amniocytes by using fluorescence in situ hybridization (FISH). Am. J. Hum. Genet. 51, 55–65.PubMedGoogle Scholar
  9. 9.
    Ward B. E., Gersen S. L., Carelli M. P., et al. (1993) Rapid prenatal diagnosis of chromosomal aneuploidies by fluorescence in situ hybridization: clinical experience with 4,500 specimens. Am. J. Hum. Genet. 52, 954–865.Google Scholar
  10. 10.
    Koch J., Kovarra S., Gregersen N., Petersen K. B., and Bolund L. (1989) Oligonucleotide-priming methods for the chromosome-specific labeling of alpha satellite DNA in situ. Chromosoma 98, 259–262.PubMedCrossRefGoogle Scholar
  11. 11.
    Heng H. H. Q., Squire J., and Tsui L.-C. (1992) High resolution mapping of mammalian genes by in situ hybridization to free chromatin. Proc. Natl. Acad. Sci. USA 89, 9509–9513.PubMedCrossRefGoogle Scholar
  12. 12.
    Heiskanen M., Hellsten E., Kallioniemi O.-P., et al. (1995) Visual mapping by fiber-FISH. Genomics 30, 31–36.PubMedCrossRefGoogle Scholar
  13. 13.
    Kallioniemi A., Kallioniemi O. P., Suder D., et al. (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258, 818–821.PubMedCrossRefGoogle Scholar
  14. 14.
    Su Y., Trent J., Guan X. Y., and Meltzer P. (1994) Direct isolation of genes encoded within a homogeneously staining region by chromosome microdissection. Proc. Natl. Acad. Sci. USA 91, 9121–9125.PubMedCrossRefGoogle Scholar
  15. 15.
    Guan X. Y., Meltzer P., Dalton W., and Trent J. (1994) Identification of cryptic sites of DNA sequence amplification in human breast cancer by chromosome microdissection. Nat. Genet. 8, 155–160.PubMedCrossRefGoogle Scholar
  16. 16.
    Schröck E., du Manoir S., Veldman T., et al. (1996) Multicolor spectral karyotyping of human chromosomes. Science 273, 494–497.PubMedCrossRefGoogle Scholar
  17. 17.
    Speicher M. R., Ballard S. G., and Ward D. C. (1996) Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nat. Genet. 12, 368–375.PubMedCrossRefGoogle Scholar
  18. 18.
    Eils R., Uhring S., Saracoglu K., et al. (1998) An optimized, fully automated system for fast and accurate identification of chromosome rearrangements by multiplex-FISH (M-FISH). Cytogenet. Cell Genet. 82, 160–171.PubMedCrossRefGoogle Scholar
  19. 19.
    Müller S., Rocchi M., Ferguson-Smith M. A., and Wienberg J. (1997) Toward a multicolor chromosome bar code for the entire human karyotype by fluorescence in situ hybridization. Hum. Genet. 100, 271–278.PubMedCrossRefGoogle Scholar
  20. 20.
    Knight S. J. L., Horsley S. W., Regan R., et al. (1997) Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres. Eur. J. Hum. Genet. 5, 1–8.PubMedGoogle Scholar
  21. 21.
    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, 207–211.PubMedCrossRefGoogle Scholar
  22. 22.
    Pollack J. R., Perou C. M., Alizadeh A. A., et al. (1999) Genome-wide analysis of DNA copy-number changes using cDNA microarrays. Nat. Genet. 23, 41–46.PubMedCrossRefGoogle Scholar
  23. 23.
    Cremer T., Lichter P., Borden J., Ward D. C., and Manuelidis L. (1988) Detection of chromosome aberrations in metaphase and interphase tumor cells by in situ hybridization using chromosome-specific library probes. Hum. Genet. 80, 235–246.PubMedCrossRefGoogle Scholar
  24. 24.
    Lichter P., Ledbetter S. A., Ledbetter D. H., and Ward D. C. (1990) Fluorescence in situ hybridization with ALU and Li polymerase chain reaction probes for rapid characterization of human chromosomes in hybrid cell lines. Proc. Natl. Acad. Sci. USA 85, 9138–9142.Google Scholar
  25. 25.
    Guan X. Y., Meltzer P., and Trent J. (1994) Rapid generation of whole chromosome painting probes (WCPs) by chromosome microdissection. Genomics 22, 101–107.PubMedCrossRefGoogle Scholar
  26. 26.
    Joyce C. A., Ross F. M., Dennis N. R., Wyre N. D., and Barber J. C. (1999) Multipaint FISH: a rapid and reliable way to define cryptic and complex abnormalities. Clin. Genet. 56, 192–199.PubMedCrossRefGoogle Scholar
  27. 27.
    Veldman T., Vignon C., Schröck E., Rowley J. D., and Ried T. (1997) Hidden chromosome abnormalities in hematological malignancies detected by multicolor spectral karyotyping. Nat. Genet. 15, 406–410.PubMedCrossRefGoogle Scholar
  28. 28.
    Sawyer J. R., Lukacs J. L., Munshi N., et al. (1998) Identification of new nonrandom translocations in multiple myeloma with multicolor spectral karyotyping. Blood 92, 4269–4278.PubMedGoogle Scholar
  29. 29.
    Rowley J. D., Reshmi S., Carlson K., and Roulston D. (1999) Spectral karyotype analysis of T-cell acute leukemia. Blood 93, 2038–2042.PubMedGoogle Scholar
  30. 30.
    Schröck E., Veldman T., Padilla-Nash H., et al. (1997) Spectral karyotyping refines cytogenetic diagnosis of constitutional chromosomal abnormalities. Hum. Genet. 101, 255–262.PubMedCrossRefGoogle Scholar
  31. 31.
    Huang B., Ning Y., Lamb A. N., Sandlin C. J., Jamehdor M., Ried T., and Bartley J. (1998) Identification of an unusual marker chromosome by spectral karyotyping. Am J. Med. Genet. 8, 368–372.CrossRefGoogle Scholar
  32. 32.
    Fan Y. S., Siu V.M, Jung J. H., and Xu J. (2000) Sensitivity of multiple color spectral karyotyping in detecting small interchromosomal rearrangements. Genetic Testing 4, 9–14.PubMedCrossRefGoogle Scholar
  33. 33.
    Weiss M. M., Hermsen M. A. J. A., Meijer G. A., et al. (1999) Comparative genomic hybridization. J. Clin. Pathol. (Mol. Pathol.) 52, 243–251.CrossRefGoogle Scholar
  34. 34.
    Levy B., Dunn T. M., Kaffe S., Kardon N., and Hirschhorn K. (1998) Clinical applications of comparative genomic hybridization. Genet. Med. 1, 4–12.PubMedCrossRefGoogle Scholar
  35. 35.
    Velagaleti G. V. N., Tharapel S. A., and Tharapel A. T. (1999) Validation of primed in situ labeling (PRINS) for interphase analysis: Comparative studies with conventional fluorescence in situ hybridization and chromosome analysis. Cancer Genet. Cytogenet. 108, 100–106.PubMedCrossRefGoogle Scholar
  36. 36.
    Pellestor F., Andréo B., and Coullin P. (1999) Interphase analysis of aneuploidy in cancer cell lines using primed in situ labeling. Cancer Genet. Cytogenet. 111, 111–118.PubMedCrossRefGoogle Scholar
  37. 37.
    Zhao L., Hayes K., and Glassman A. (2000) Enhanced detection of chromosomal abnormalities with the use of RxFISH multicolor banding technique. Cancer Genet. Cytogenet. 118, 108–111.PubMedCrossRefGoogle Scholar
  38. 38.
    Knight S. J. L., Lese C. M., Precht K. S., et al. (2000) An optimized set of human telomere clones for studying telomere integrity and architecture. Am. J. Hum. Genet. 67, 320–332.PubMedCrossRefGoogle Scholar
  39. 39.
    Vaandrager J. W., Schuuring E., Zwikstra E., et al. (1996) Direct visualization of dispersed 11q13 chromosomal translocations in mantle cell lymphoma by multicolor DNA fluorescence in situ hybridization. Blood 88, 1177–1182.PubMedGoogle Scholar
  40. 40.
    McDonell N., Ramser J., Francis F., et al. (2000) Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia. Genomics 15, 221–229.CrossRefGoogle Scholar
  41. 41.
    Suto Y., Ishikawa Y., Hyodo H., Uchikawa M., and Juji T. (2000) Gene organization and rearrangements at the human Rhesus blood group locus revealed by fiber-FISH analysis. Hum. Genet. 106, 164–171.PubMedCrossRefGoogle Scholar
  42. 42.
    Weber-Matthiesen K., Winkemann M., Müller-Hermelink A., Schlegelberger B., and Grote W. (1992) Simultaneous fluorescence immunophenotyping and interphase cytogenetics: A contribution to the characterization of tumor cells. J. Histochem. Cytochem. 40, 171–175.PubMedGoogle Scholar
  43. 43.
    Takahashi N., Miura I., Saitoh K., and Miura A. B. (1998) Lineage involvement of stem cells bearing the Philadelphia chromosome in chronic myeloid leukemia in the chronic phase as shown by a combination of fluorescence-activated cell sorting and fluorescence in situ hybridization. Blood 92, 4758–4763.PubMedGoogle Scholar
  44. 44.
    Zhang Y., Wong K. F., Siebert R., Matthiesen P., and Harder S. (1999) Chromosome aberrations are restricted to the CD56+, CD3-, tumor cell population in natural killer cell lymphomas: A combined immunophenotyping and FISH study. Br. J. Haematol. 105, 737–742.PubMedCrossRefGoogle Scholar
  45. 45.
    American Society of Human Genetics/ American College of Medical Genetics Test and Technology Transfer Committee (1996) Diagnostic testing for Prader-Willi and Angelman syndromes: Report of the ASHG/ACMG Test and Technology Transfer Committee. Am. J. Hum. Genet. 58, 1085–1088.Google Scholar
  46. 46.
    Posenberg M. J., Vaske D., Killoran C. E., et al. (2000): Detection of chromosomal aberration by a whole-genome microsatellite screen. Am. J. Hum. Genet. 66, 419–427.CrossRefGoogle Scholar
  47. 47.
    Colleaux L., Rio M., Heuertz S., et al. (2000), A novel automated strategy for screening cryptic telomeric rearrangements in children with idiopathic mental retardation. Am. J. Hum Genet. 67, Abstract 257.Google Scholar
  48. 48.
    Bubendorf L., Kononen J., Koivisto P., et al. (1999), Survey of gene amplifications during prostate cancer progression by high-throughput fluorescence in situ hybridization on tissue microarrays. Cancer Res. 59, 803–806.PubMedGoogle Scholar
  49. 49.
    Snijders A. M., Hindle A. K., Segraves R., et al. (2000), Quantitative DNA copy number analysis across the human genome with ~1 megabase resolution using array CGH. Am. J. Hum. Genet. 67, Abstract 112.Google Scholar
  50. 50.
    Nora J. J., Fraser F. C., Bear J., Greenberg C. R., Patterson D., and Warburton D., ed. (1994) Medical Genetics. 4th ed, Lea and Febiger, Malvern, PA, 36.Google Scholar
  51. 51.
    Fan Y. S., Rizkalla K., and Barr R. M. (1999) Complex rearrangement of chromosomes 1, 7, and 16 in chronic myelomonocytic leukemia. Cancer Genet. Cytogenet. 112, 190–192.PubMedCrossRefGoogle Scholar
  52. 52.
    Fan Y. S., Rizkalla K., and Engel J. (1999) Interstitial deletion of 8(q13q22) in diffuse large B-cell gastric lymphoma. Cancer Genet. Cytogenet. 115, 28–31.PubMedCrossRefGoogle Scholar
  53. 53.
    Fan Y. S., Rizkalla K., Brien F. W., and Engel C. J. (2000) Jumping translocations of 11q in acute myeloid leukemia and 1q in follicular lymphoma. Cancer Genet. Cytogenet. 118, 35–41.PubMedCrossRefGoogle Scholar
  54. 54.
    Jalal S. M. and Law M. E. (1999) Utility of multicolor fluorescent in situ hybridization in clinical cytogenetics. Genet. Med. 5, 181–186.Google Scholar
  55. 55.
    Fleischman E. W., Reshmi S., Frenkel M. A., et al. (1999) MLL is involved in a t(2;11)(p21;q23) in a patient with acute myeloblastic leukemia. Genes Chromosomes Cancer 24, 151–155.PubMedCrossRefGoogle Scholar
  56. 56.
    Aventín A., La Starza R., Martínez C., et al. (1999) Involvement of MLL gene in a t(10;11)(q22;q23) and a t(8;11)(q24;q23) identified by fluorescence in situ hybridization. Cancer Genet. Cytogenet. 108, 48–52.PubMedCrossRefGoogle Scholar
  57. 57.
    Fan Y. S., Jung J., and Hamilton B. (1999) Small terminal deletion of 1p and duplication of 1q: cytogenetics, FISH studies, and clinical observations at newborn and at age 16 years. Am. J. Med. Genet. 86, 118–123.PubMedCrossRefGoogle Scholar
  58. 58.
    Fan Y. S., Rizkalla K., and Barr R. M. (1999) A new complex variant Philadelphia chromosome, t(1;9;22)ins(17;22), characterized by fluorescence in situ hybridization in an adult ALL. Leuk. Res. 23, 1001–1006.PubMedCrossRefGoogle Scholar
  59. 59.
    Fan Y. S. and Siu V. M. (2001) Molecular cytogenetic characterization of a derivative chromosome 8 with an inverted duplication of 8p21.3->p23.3 and a rearranged duplication of 8q24.13->qter. Am. J. Med. Genet. 102, 266–271.PubMedCrossRefGoogle Scholar
  60. 60.
    Shapira S. K. (1998) An update on chromosome deletion and microdeletion syndromes. Current Opinion in Pediatrics 10, 622–627.PubMedCrossRefGoogle Scholar
  61. 61.
    Swillen A., Vogels A., Devriendt K., and Fryns J. P. (2000) Chromosome 22q11 deletion syndrome: update and review of the clinical features, cognitive-behavioral spectrum, and psychiatric complications. Am. J. Med. Genet. (Semin. Med. Genet.) 97, 128–135.CrossRefGoogle Scholar
  62. 62.
    Du Montcel S. T., Mendizabal H., Aymé S., Lévy A., and Philip N. (1996) Prevalence of 22q11 microdeletion. J. Med. Genet. 33, 719.CrossRefGoogle Scholar
  63. 63.
    Devriendt K., Fryns J. P., Mortier G., van Thienen M. N., and Keymolen K. (1998) The annual incidence of DiGeorge/velocardiofacial syndrome. J. Med. Genet. 35, 789–790.PubMedCrossRefGoogle Scholar
  64. 64.
    Shapira S. K., McCaskill C., Northrup H., et al. (1997) Chromosome 1p36 deletions: The clinical phenotype and molecular characterization of a common newly delineated syndrome. Am. J. Hum. Genet. 61, 642–650.PubMedCrossRefGoogle Scholar
  65. 65.
    Fan Y. S., Cairney A. E., and Siu V. M. (1997) Polyslenia and neutropenia in a patient with 22q11 deletion and trichorhinophalangeal syndrome. Am. J. Hum. Genet. 61, Supplement A97.Google Scholar
  66. 66.
    Fan Y. S. and Farrell S. A. (1994) Prenatal diagnosis of interstitial deletion of 17(p11.2p11.2) (Smith-Magenis syndrome). Am. J. Med. Genet. 49, 253–254.PubMedCrossRefGoogle Scholar
  67. 67.
    Flint J., Wilkie A. O. M., Buckle V. J., Winter R. M., Holland A. J., and McDermid H. E. (1995) The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat. Genet. 9, 132–140.PubMedCrossRefGoogle Scholar
  68. 68.
    Knight S. J. L. and Flint J. (2000) Perfect endings: a review of subtelomeric probes and their use in clinical diagnosis. J. Med. Genet. 37, 401–409.PubMedCrossRefGoogle Scholar
  69. 69.
    Knight S. J. L., Regan R., Nicod A., et al. (1999) Subtle chromosomal rearrangements in children with unexplained mental retardation. Lancet 354, 1676–1681.PubMedCrossRefGoogle Scholar
  70. 70.
    Fan Y. S., Yang Z., Speevak M., Farrell S., Jung J. H., and Siu V. M. (2001) Detection of subtelomeric aberrations in patients with unexplained mental retardation by FISH using multiple subtelomeric probes. Genetics in Medicine 20(6), 2001. 3(6), 416–421.CrossRefGoogle Scholar
  71. 71.
    Vorsanova S. G., Koloti D., Sharonin V. O., Sloviev V., and Yurov Y. B. (1998) FISH analysis of microaberrations at telomeric and subtelomeric regions in chromosomes of children with mental retardation. Am. J. Hum. Genet. 63(suppl), A169.Google Scholar
  72. 72.
    Ballif B. C., Kashork C. D., and Shaffer L. G. (2000) The promise and pitfalls of telomere region-specific probes. Am. J. Hum. Genet. 67, 1356–1359.PubMedGoogle Scholar
  73. 73.
    Eiben B., Trawicki W., Hammons W., Goebel R., Pruggmayer M., and Epplen J. T. (1999) Rapid prenatal diagnosis of aneuploidies in uncultured amniocytes by fluorescence in situ hybridization. Evaluation of >3,000 cases. Fetal Diagn. Ther. 14, 193–197.PubMedCrossRefGoogle Scholar
  74. 74.
    Lewin P., Kleinfinger P., Bazin A., Mossafa H., and Szpiro-Tapia S. (2000) Defining the efficiency of fluorescence in situ hybridization on uncultured amniocytes on a retrospective cohort of 27,407 prenatal diagnosis. Prenat. Diagn. 20, 1–6.PubMedCrossRefGoogle Scholar
  75. 75.
    Feldman B., Ebrahim S. A. D., Hazan S. L., et al. (2000) Routine prenatal diagnosis of aneuploidy by FISH studies in high-risk pregnancies. Am. J. Med. Genet. 90, 233–238.PubMedCrossRefGoogle Scholar
  76. 76.
    Steele C. D., Wapner R. J., Smith J. B., Haynes M. K., and Jackson L. G. (1996) Prenatal diagnosis using fetal cells isolated from maternal peripheral blood: A review. Clin. Obstet. Gynecol. 39, 801–813.PubMedCrossRefGoogle Scholar
  77. 77.
    Valerio D., Aíello R., Altieri V., Malato A. P., Fortunato A., and Canazio A. (1996) Culture of fetal erythroid progenitor cells from maternal blood for noninvasive prenatal genetic diagnosis. Prenat. Diagn. 16, 1073–1082.PubMedCrossRefGoogle Scholar
  78. 78.
    Mavrou A., Colialexi A., Tsangaris G. T., et al. (1998) Fetal cells in maternal blood: Isolation by magnetic cell sorting and confirmation by immunophenotyping and FISH. In Vivo 12, 195–200.PubMedGoogle Scholar
  79. 79.
    Oosterwijk J. C., Mesker W. E., Ouwerkerk-van Velzen M. C., et al. (1998) Development of a preparation and staining method for fetal erythroblasts in maternal blood: Simultaneous immunocytochemical staining and FISH analysis. Cytometry 32, 170–177.PubMedCrossRefGoogle Scholar
  80. 80.
    Al-Mufti R., Hambley H., Farzaneh F., and Nicolaides K. H. (1999) Investigation of maternal blood enriched for fetal cells: Role in screening and diagnosis of fetal trisomies. Am. J. Med. Genet. 85, 66–75.PubMedCrossRefGoogle Scholar
  81. 81.
    Yang Y. H., Jee K. J., Kim S. K., et al. (2000) Prenatal genetic diagnosis from maternal blood: Simultaneous immunophenotyping and FISH of fetal nucleated erythrocytes isolated by negative and positive magnetic activated cell sorting. Yonsei. Med. J. 41, 258–265.PubMedGoogle Scholar
  82. 82.
    Munne S., Dailey T., Sultan K. M., Grifo J., and Cohen J. (1995) The use of first polar bodies for preimplantation diagnosis of aneuploidy. Hum. Reprod. 10, 1014–1020.PubMedGoogle Scholar
  83. 83.
    Verlinsky Y., Cieslak J., Ivakhnenko V., Lifchez A., Strom C., and Kuliev A. (1996) Birth of healthy children after preimplantation diagnosis of common aneuploidies by polar body fluorescence in situ hybridization analysis. Fertil. Steril. 66, 126–129.PubMedGoogle Scholar
  84. 84.
    Verlinsky Y., Cieslak J., Ivakhnenko V., et al. (1998) Preimplantation diagnosis of common aneuploidies by the first-and second-polar body FISH analysis. J. Assist. Reprod. Genet. 15, 285–289.PubMedCrossRefGoogle Scholar
  85. 85.
    Verlinsky Y., Cieslak J., Ivakhnenko V., et al. (1999) Prevention of age-related aneuploidies by polar body testing of oocytes. J. Assist. Reprod. Genet. 16, 165–169.PubMedCrossRefGoogle Scholar
  86. 86.
    Liu J., Tsai Y. L., Zheng X. Z., et al. (1998) Feasibility study of repeated fluorescence in situ hybridization in the same human blastomeres for preimplantation genetic diagnosis. Mol. Hum. Reprod. 4, 972–977.PubMedCrossRefGoogle Scholar
  87. 87.
    Munne S., Magli C., Bahce M., et al. (1998) Preimplantation diagnosis of the aneuploidies most commonly found in spontaneous abortions and live births: XY, 13, 14, 15, 16, 18, 21, 22. Prenat. Diagn. 18, 1459–1466.PubMedCrossRefGoogle Scholar
  88. 88.
    Gianaroli L., Magli M. C., Ferraretti A. P., and Munne S. (1999) Preimplantation diagnosis for aneuploidies in patients undergoing in vitro fertilization with a poor prognosis: Identification of the categories for which it should be proposed. Fertil. Steril. 72, 837–844.PubMedCrossRefGoogle Scholar
  89. 89.
    Kalousek D. K. (2000) Pathogenesis of chromosomal mosaicism and its effect on early human development. Am. J. Med. Genet. 91, 39–45.PubMedCrossRefGoogle Scholar
  90. 90.
    Lomax B., Kalousek D. K., Kuchinka B., Barrett I. J., Harrison K.J, and Safavi H. (1994) The utilization of interphase cytogenetic analysis for the detection of mosaicism. Hum. Genet. 93, 243–247.PubMedCrossRefGoogle Scholar
  91. 91.
    Lestou V. S., Lomax B., Barrett I. J., and Kalousek D. K. (1999) Screening of human placentas for chromosomal mosaicism using comparative genomic hybridization. Teratology 59, 325–330.PubMedCrossRefGoogle Scholar
  92. 92.
    Robinson W. P., Barrett I. J., Bernard L., et al. (1997) Meiotic origin of trisomy in CPM is correlated with presence of fetal uniparental disomy, high levels of trisomy in trophoblast, and increased risk of fetal intrauterine growth restriction. Am. J. Hum. Genet. 60, 917–927.PubMedGoogle Scholar
  93. 93.
    Block A. W. (1999) Cancer Cytogenetics, in The Principles of Clinical Cytogenetics, (Gersen S. L. and Keagle M. B., eds.), Humana Press, Totowa, NJ, 345–420.Google Scholar
  94. 94.
    Dewald G. W., Wyatt W. A., Junaeu A. L., et al. (1998) Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia. Blood 91, 3357–3365.PubMedGoogle Scholar
  95. 95.
    Bu~no I., Wyatt W. A., Zinsmeister A. R., Dietz-Band J., Silver R. T., and Dewald G. W. (1998) A special fluorescence in situ hybridization technique to study peripheral blood and assess the effectiveness of interferon therapy in chronic myeloid leukemia. Blood 92, 2315–2321.Google Scholar
  96. 96.
    Dewald G., Stallard R., Alsaadi A., et al. (2000) A multicenter investigation with D-FISH BCR/ABL1 probes. Cancer Genet. Cytogenet. 116, 97–104.CrossRefGoogle Scholar
  97. 97.
    Rafi S. K., El Gebaly H., and Qumsiyeh M. B. (2000): ETV6/CBFA2 fusions in childhood B-cell precursor acute lymphoblastic leukemia with myeloid markers. Diagn. Mol. Pathol. 9, 184–189.PubMedCrossRefGoogle Scholar
  98. 98.
    Loh M. L., Samson Y., Motte E., et al. (2000) Translocation (2;8)(p12;q24) associated with a cryptic t(12;21)(p13:q22) TEL/AML1 gene rearrangement in a child with acute lymphoblastic leukemia. Cancer Genet. Cytogenet. 15, 79–82.CrossRefGoogle Scholar
  99. 99.
    Vaandrager J. W., Schuuring E., Raap T., Phillippo K., Kleiverda K., and Kluin P. (2000) Interphase FISH detection of BCL2 rearrangement in follicular lymphoma using breakpoint-flanking probes. Genes Chromosomes Cancer 27, 85–94.PubMedCrossRefGoogle Scholar
  100. 100.
    Yang P., Hirose T., Hasegawa T., Hizawa K., and Sano T. (1998) Dual-color fluorescence in situ hybridization analysis of synovial sarcoma. J. Pathol. 184, 7–13.PubMedCrossRefGoogle Scholar
  101. 101.
    Kumar S., Pack S., Kumar D., et al. (1999) Detection of EWS-FLI-1 fusion in Ewing’s sarcoma/peripheral primitive neuroectodermal tumor by fluorescence in situ hybridization using formalin-fixed paraffin-embedded tissue. Hum. Pathol. 30, 324–330.PubMedCrossRefGoogle Scholar
  102. 102.
    Schofield D. E. and Fletcher J. A. (1992) Trisomy 12 in pediatric granulosa-stromal cell tumors: demonstration by a modified method of fluorescence in situ hybridization on paraffin-embedded material. Am. J. Pathol. 141, 1265–1269.PubMedGoogle Scholar
  103. 103.
    Xiao S., Renshaw A., Cibas E. S., Hudson T. J., and Fletcher J. A. (1995) Novel fluorescence in situ hybridization approaches in solid tumors. Am. J. Pathol. 147, 896–904.PubMedGoogle Scholar
  104. 104.
    Blough R. I., Heerema N. A., Ulbright T. M., Smolarek T. A., Roth L. M., and Einhorn L. H. (1998) Interphase chromosome painting of paraffin-embedded tissue in the differential diagnosis of possible germ cell tumors. Med. Pathol. 11, 634–641.Google Scholar
  105. 105.
    Wettengel G. V., Draeger J., Kiesewetter F, Schell H., Neubauer S., and Gebhart E. (1999) Differentiation between Spitz nevi and malignant melanomas by interphase fluorescence in situ hybridization. Int. J. Oncol. 14, 1177–1183.PubMedGoogle Scholar
  106. 106.
    Brown J.A, Slezak J. M., Lieber M. M., and Jenkins R. B. (1999) Fluorescence in situ hybridization aneuploidy as a predictor of clinical disease recurrence and prostate-specific antigen level 3 years after radical prostatectomy. Mayo Clin. Proc. 74, 1214–1220.PubMedCrossRefGoogle Scholar
  107. 107.
    Perlman E. J., Hu J., Ho, D., Cushing B., Lauer S., and Castleberry R. P. (2000) Genetic analysis of childhood endodermal sinus tumors by comparative genomic hybridization. J. Pediatr. Hematol. Oncol. 22, 100–105.PubMedCrossRefGoogle Scholar
  108. 108.
    Shpiro D. N., Valentine M. B., Rowe S. T., et al. (1993) Detection of in situ gene amplification by fluorescence in situ hybridization: Diagnostic utility for neuroblastoma. Am. J. Pathol. 142, 1339–1346.Google Scholar
  109. 109.
    Tajiri T., Shono K., Fujii Y., et al. (1999) Highly sensitive analysis for in situ amplification in neuroblastoma based on fluorescence in situ hybridization. J. Pediatr. Surg. 34, 1615–1619.PubMedCrossRefGoogle Scholar
  110. 110.
    Komuro H., Valentine M. B., Rowe S. T., Kidd V. J., Makino S., Brodeur G. M., Cohn S. L., and Look A. T. (1998) Fluorescence in situ hybridization analysis of chromosome 1p36 deletion in human MYCN amplified neuroblastoma. J. Pediatr. Surg. 33, 1695–1898.PubMedCrossRefGoogle Scholar
  111. 111.
    Jacobs T. W., Gown A. M., Yaziji H., Barnes M. J., and Schnitt S. J. (1999) Comparison of fluorescence in situ hybridization and immunohistochemistry for the evaluation of HER-2/neu in breast cancer. J. Clin. Oncol. 17, 1974–1982.PubMedGoogle Scholar
  112. 112.
    Jimenez R. E., Wallis T., Tabasczka P., and Visscher D. W. (2000) Determination of Her-2/Neu status in breast carcinoma: Comparative analysis of immunohistochemistry and fluorescence in situ hybridization. Mod. Pathol. 13, 37–45.PubMedCrossRefGoogle Scholar
  113. 113.
    Pauletti G., Dandekar S., Rong H., et al. (2000) Assessment of methods for tissuebased detection of the HER-2/neu alteration in human breast cancer: A direct comparison of fluorescence in situ hybridization and immunohistochemistry. J. Clin. Oncol. 18, 3651–3664.PubMedGoogle Scholar
  114. 114.
    Hoang M. P., Sahin A. A., Ordonez N. G., and Sneige N. (2000) HER-2/neu gene amplification compared with HER-2/neu protein overexpression and interobserver reproducibility in invasive breast carcinoma. Am. J. Clin. Pathol. 113, 852–859.PubMedCrossRefGoogle Scholar
  115. 115.
    Wang S., Saboorian M. H., Frenkel E., Hynan L., Gokaslan S. T., and Ashfaq R. (2000) Laboratory assessment of the status of Her-2/neu protein and oncogene in breast cancer specimens: Comparison of immunohistochemistry assay with fluorescence in situ hybridization assays. J. Clin. Pathol. 53, 374–381.PubMedCrossRefGoogle Scholar
  116. 116.
    Ridolfi R. L., Jamehdor M. R., and Arber J. M. (2000) HER-2/neu testing in breast carcinoma: A combined immunohistochemical and fluorescence in situ hybridization approach. Mod. Pathol. 13, 866–873.PubMedCrossRefGoogle Scholar
  117. 117.
    American College of Medical Genetics (1993) Prenatal interphase fluorescence in situ hybridization (FISH) policy statement. Am. J. Hum. Genet. 635, 526–527Google Scholar
  118. 118.
    American College of Medical Genetics (1996) Standards and Guidelines for Clinical Genetics Laboratories. Bethesda, MD.Google Scholar
  119. 119.
    American College of Medical Genetics (1999) Standards and Guidelines for Clinical Genetics Laboratories, 2nd ed. Bethesda, MD. Also at
  120. 120.
    The CCMG Cytogenetics Committee [Coté, Dallaire, Fan, Horsman, Kalousek, Tomkins, Roland (Chair)] (1997) CCMG position statement on the clinical application of fluorescence in situ hybridization. CCMG Newsletter 1997 (3), 3–6.Google Scholar
  121. 121.
    Test and Technology Transfer Committee (2000) Technical and clinical assessment of fluorescence in situ hybridization: An ACMG/ASHG position statement. I. Technical considerations. Genet. Med. 2, 358–361.Google Scholar

Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • Yao-Shan Fan
    • 1
  1. 1.Cytogenetics DivisionLondon Health Sciences Center and The University of Western OntarioLondonCanada

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