CytoScan Microarray for genome-wide copy number assessment for CLL, MDS

Test Description

Detection of chromosomal aberrations in CLL/MDS by DNA copy number analysis



Cytogenetic abnormalities are fairly common (60-85%) in chronic lymphocytic leukemia/small lymphocytic lymphoma (1-9). Deletions of the long arm of chromosome 6 have been identified by classical cytogenetics and FISH in up to 7% of B-cell CLL (1,2). It appears that the deletion of 6q chromosome is associated with a high incidence of atypical morphology and has an intermediate prognosis in B-cell CLL (7-9). Deletion of chromosome 11q is detected in about 5–20% of CLL patients and is highly variable in size (>20 Mb in most cases). The minimal deleted region includes 11q22.3- q23.1, harboring ATM gene in almost all cases. CLL cases with this abnormality are characterized by large and multiple lymphadenopathies and have been reportedly associated with other poor prognostic markers, such as unmutated IGHV genes, shorter remission durations, and shorter overall survival following standard chemotherapy (4,5). Trisomy of chromosome 12 is seen in 10–20% of cases of CLL. The patients with trisomy of chromosome 12 tend to have an intermediate to low risk for disease progression (1,4). Deletion of chromosome region 13q14, found in more than 50% of CLL patients, is the most common cytogenetic abnormality. Isolated small 13q deletion, which often involves miR-15a/miR16-1 cluster but not RB1 locus, is a good prognostic marker. Large 13q deletion involving RB1 gene has been reported to be associated with shorter time to first treatment (TTFT) and overall survival (3,4). Deletion of 17p is found in approximately 3–8% of CLL patients at diagnosis and is one of the most frequently acquired aberrations status post therapy (up to 30% of chemotherapy refractory CLL). These patients are considered to have the highest risk for disease progression, as shown to have the shortest overall survival and progression free survival (1,6).


Clonal chromosomal abnormalities can be detected in approximately 50% of patients with de novo MDS and in over 90% of patients with therapy-related myeloid neoplasms. AML with myelodysplasia-related changes demonstrates chromosomal abnormalities similar to those seen in MDS (10). Identification of specific cytogenetic abnormalities is an important part of the Revised International Prognostic Scoring System (IPSS-R) for MDS (11). As a sole karyotypic abnormality, del(5q) defines a distinct WHO 2008 category of MDS with isolated del(5q), and signals a favorable prognosis. MDS patients with del(5q) may respond to lenalidomide therapy (10). In the absence of morphologic criteria diagnostic of MDS, the presence of +8, -Y, or del(20q) as a sole cytogenetic abnormality is not considered definitive evidence of MDS (11). Correlation with classical cytogenetic and/or FISH studies is recommended to exclude additional cytogenetic abnormalities that may not be detected with this assay.


For fresh peripheral blood or bone marrow samples, genomic DNA is isolated using standard laboratory procedure. DNA quantity and quality is evaluated by spectrophotometric analysis. DNA is analyzed for copy number alterations using Affymetrix Cytoscan HD assay as per manufacturer’s instructions. Raw data files (CEL files) are generated from Affymetrix Molecular Diagnostics Software (AMDS) (Affymetrix Inc., Santa Clara, CA). To analyze copy number variations, the CEL files are imported into Chromosome Analysis Suite v3.0 (Affymetrix, Inc, CA) to generate copy number gain and loss using GRCh37 (hg19) human genome reference. Cytoscan HD library reference files provided by Affymetrix are used as a baseline. Appropriate QC metrics are reviewed to verify overall sample quality and data integrity. The analyzed copy number data from the CHYP files are reviewed using a Graphic User Interface (GUI) tool in Chromosome Analysis Suite v3.0 (Affymetrix, Inc, CA) for clinical interpretation. The limit of detection is 20-25% of cells with genetic alteration.

Specimen Requirements

  • Peripheral Blood: 3-5 mL, collected in EDTA (purple top) tube, store at room temperature 24 hours
  • Bone Marrow: 0.5-1mL, collected in EDTA (purple top) tube, stored at room temperature 24 hours.

Turnaround Time

Results reported within 7-20 business days



Shipment Must Include

Requisition form
Patient pathology report


  1. Rodríguez-Vicente AE et al. Chronic lymphocytic leukemia: a clinical and molecular heterogenous disease. Cancer Genet. 2013 Mar;206(3):49-62.
  2. Baliakas P, et al, Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: a systematic reappraisal of classic cytogenetic data. Am J Hematol. 2014;89(3):249-55.
  3. Ouillette P, et al. The prognostic significance of various 13q14 deletions in chronic lymphocytic leukemia. Clin Cancer Res. 2011;17(21):6778-90.
  4. Rossi D, et al. Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. Blood. 2013;121(8):1403-12.
  5. Wierda WG, et al. Multivariable model for time to first treatment in patients with chronic lymphocytic leukemia. J Clin Oncol. 2011;29(31):4088-95.
  6. Wawrzyniak E, et al. Clonal evolution in CLL patients as detected by FISH versus chromosome banding analysis, and its clinical significance. Eur J Haematol. 2014 Feb;92(2):91-101
  7. Offit K, et al. Clinical and morphologic features of B-cell small lymphomacytic lymphoma with del(6)(q21q23). Blood. 1994 May 1;83(9):2611-8
  8. Stilgenbauer S, et al. Incidence and clinical significance of 6q deletions in B cell chronic lymphocytic leukemia. Leukemia 1999; 13:1331-1334.
  9. Cuneo A, et al. Chronic lymphocytic leukemia with 6q- shows distinct hematological features and intermediate prognosis. Leukemia. 2004 Mar;18(3):476-83.
  10. Swerdlow SH, Campo E, Harris NL, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2008.
  11. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012;120:2454-2465.