Indiana University School of Medicine - PDF document

1 Indiana University School of Medicine
Indiana University School of Medicine Division of Diagnostic Genomics - Cytogenetics Laboratory 975 West Walnut Street, IB2 65 Indianapolis, IN. 46202 - 5251 Tel. 317 - 274 - 2243 Neoplastic Chromosome Analysis – Bone Marrow, Peripheral Blood , Bone Core or Tumors Chromosome Analysis for Neoplastic Disorders Clinical Background  Clonal genetic abnormalities are a hallmark of malignant neoplasms and a wide range of these abnormalities can be identified by cytogenetic studies.  Chromosome abnormalities have been reported in many human neoplasms.  In hematologic disorders, chromosomal abnormalities play an important role in the pathogenesis, prognosis, diagnosis, treatment selection and in monitoring treatment response and remission in patients .  Cytogenetic analysis to identify an abnormal clone consistently associated with a neoplasm is used in determining the staging of solid tumors.  Chromosomal abnormalities are used to classify various neoplastic disorders.  Companion fluorescence in - situ hybridization (FISH) testing with appropriate probe sets may f urther delineate chromosome abnormalities and assess minimal residual disease. Epidemiology Table 1. Incidence of representative neoplastic disorders. Disease Incidence (Worldwide) Chronic Myeloid Leukemia (CML) 1 - 2/100,000 Polycythemia vera 0.7 - 2.6/100,000 (increases with age) Myelodysplastic Syndrome s 5/100,000 Acute Myeloid Leukemia (AML) 3/100,000 (adults) ; 0.7/100,000 (children) Chronic Lympho cytic Leukemia (CLL) 2 - 6 /100,000 Acute Lymphoblastic Leukemia (ALL) 1 - 4.75/100,000 Non - Hodgkin Lymphoma ~ 70,000 diagnosed annually Monoclonal Gammopathy Undetermined Significance (MGUS) 1 - 2/100 in pati�ents

2 50 years Plasma Cell Myeloma (Multi
50 years Plasma Cell Myeloma (Multiple Myeloma) 3 - 9/100,000 Neuroblastoma 10.5/100,000 Ewing Sarcoma 4/100,000 Rhabdomyosarcoma 2 - 4/100,000 Indiana University School of Medicine Division of Diagnostic Genomics - Cytogenetics Laboratory 975 West Walnut Street, IB2 65 Indianapolis, IN. 46202 - 5251 Tel. 317 - 274 - 2243 Genetics  Chromosome abnormalities are acquired during the neoplastic process. These abnormalities are found in the tumor cells . Abnormalities may be associated with chromosome rearrangement and include structural changes such as translocations, deletions, duplications or other abnormalities.  Abnormal segregation during mitosis as a result of nondisjunction or other error s in cell division may produce monosomies, trisomies or ploidy changes.  Certain acquired abnormalities are indicative of specific diseases. Indications for Ordering  Newly diagnosed hematopoietic disorders  Follow up of hematopoietic disorders  Newly diagnosed neo plastic disorders  Staging of other neoplastic disorders Interpretation  A range of chromosome abnormalities are specifically associated with certain types of cancers.  Presence of a normal karyotype however does not eliminate the possibility of an underlying neoplas tic mutation . S ubmicroscopic abnormalities may be present which cannot be detected by chromosome analysis.  In a small number of cases, a chromosomal abnormality may be associated with a congenital disorder which may not be related to the neoplastic process. Consultation with a medical genetics professional is recommended in these cases.  Availability of clinical information facilitate s in determining the appropriate type of cy

3 togenetic study to be performed and ens
togenetic study to be performed and ensures an accurate inter pretation of the test.  Limitations: This analysis does not eliminate the possibility of low frequency mosaicism or small structural abnormalities. Living cells are required for chromosome analysis. As such, sample quality can affect the turnaround time . Methodology Indiana University School of Medicine Division of Diagnostic Genomics - Cytogenetics Laboratory 975 West Walnut Street, IB2 65 Indianapolis, IN. 46202 - 5251 Tel. 317 - 274 - 2243  Tissue culture of neoplastic cells in appropriate culture medium, followed by metaphase chromosome preparation, G - banding of chromosomes and microscopic or computer analysis of available metaphases at 400 - 500 band level are performed.  Add itional staining techniques may be utilized.  Results of companion FISH testing (if requested) are reported along with the chromosome analysis. References 1. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Fourth edition. Edited by SH S werdlow, E Campo, NL Harris, et al: Lyon, France, IARC Press, 2008 2. Mitelman F, Johansson B, Mertens F. The impact of translocations and gene fusions on cancer causation. Nature Rev Cancer. 2007; 7: 233 - 245 3. Dewald GW, Ketterling RP, Wyatt WA, Stupca PJ: Cytogenetic studies in neoplastic hematologic disorders. In Clinical Laboratory Medicine. Second edition. Edited by KD McClatchey. Baltimore, Williams and Wilkens, 2002, pp 658 - 685 4. Mitelman Database of Chromosome Aberrations in Cancer (2001). Edited b y F Mitelman, B Johansson, F Mertens; available at http://cgap.nci.nih.gov/Chromosomes/Mitelman 5. Sandberg AA, Turc - Carel C, Gemmell RM: Chromosomes in solid tumors and beyond. Cancer Res 1988;48:104 9 - 105