This Cancer Cytogenomic Array assay is performed using the Affymetrix Cytoscan HD platform. This array contains more than 2.6 million copy number markers, including 750,000 SNPs, with a median spacing of 0.88 kb within genes. Patient DNA is isolated, amplified, enzymatically fragmented, and hybridized to oligonucleotide probes. The array is washed, scanned, and the results are analyzed and interpreted using Affymetrix Chromosome Analysis Suite software (ChAS).
This Cancer Cytogenomic Array (CCA) assay detects DNA copy number gains and losses as well as regions of loss of heterozygosity (LOH) by SNP analysis. It is particularly useful as a more comprehensive replacement of FISH panels for myelodysplastic syndrome (MDS) and chronic lymphocytic leukemia (CLL), as millions of oligonucleotide probes across the genome are interrogated for gains and losses, and copy-neutral LOH is detected as well. Approximately half of patients with known MDS have a normal karyotype, and the microarray has a greater diagnostic yield than FISH panels. The CCA assay is particularly useful for malignant conditions with a low mitotic index and when limited material is available for cell culture for karyotypes. This assay also is useful in detection of clonal abnormalities to help establish a diagnosis of MDS.
Bone marrow aspirate specimens with at least 20% involvement by malignant cells are most useful for the evaluation of acute leukemia, MDS, or myeloproliferative neoplasia. Contact the laboratory to verify suitability of peripheral blood.
CLL has prognostically significant gains and losses that are difficult to detect by karyotype due to lack of mitotic activity in cell culture. FISH panels have been more informative, however, the higher resolution of a genomic microarray and the detection of LOH by SNPs provide a comprehensive overview of genetic complexity and aberrations involving clinically important loci. For example, LOH of 17p is often correlated with homozygous mutations of the TP53 locus, which are associated with a worse prognosis.
For CLL, peripheral blood specimens obtained at the time of diagnosis or with high levels of recurrent/residual leukemia are most suitable. For post-therapy testing for evolution, FISH for p53 (TP53 locus) or the CLL FISH panel is recommended. As the CCA assay does not detect balanced chromosome abnormalities, FISH analysis for the t(11;14) associated with mantle cell lymphoma should be ordered separately, if indicated (see FISH for Malignancy, or FISH for CLL Handbook listings).
Acute lymphoblastic leukemia (ALL) at diagnosis may have clinically important copy number changes revealed by microarray with SNPs. ALL karyotypes are frequently normal even when FISH demonstrates clonal abnormalities, due to the poor morphology of ALL and the resulting difficulty in obtaining analyzable metaphase cells. Many genetic abnormalities detected at diagnosis have prognostic significance and can be used to monitor response to therapy. Furthermore, sub-microscopic deletions with prognostic significance have been identified by oligonucleotide and SNP arrays; for example, IKZF1 gene deletions are associated with a poor prognosis. CDKN2A/B deletions are common, and LOH for 9p is associated with homozygous mutations of CDKN2A.
For ALL, note that clinically important balanced rearrangements would not be detected; thus, the CCA assay is complementary to the standard karyotype. Also, at least 20% blasts must be present in a peripheral blood sample, if submitted.
Interpretive report provided.
Although Cancer Cytogenomic Array is a powerful diagnostic tool for the evaluation of chromosomal copy number changes, this assay will not detect balanced chromosomal aberrations, imbalance of regions not represented on the microarray, or point mutations. Thus, this test is complementary to conventional chromosome analysis (requires a separate sample). A karyotype or FISH test is more appropriate when a translocation or inversion [e.g., t(8;21), t(9;22), t(15;17), inv(16)] is suspected. Also, chromosome or FISH analysis is more appropriate if a STAT result is required. The detection threshold for mosaicism is variable (20-30%), depending on the size of the segment. Interpretation of Cancer Cytogenomic Array results can be complicated by the detection of constitutional changes that may or may not be related to the malignancy. This may warrant genetic testing of a peripheral blood sample, and referral to a clinical geneticist for further evaluation and counseling.
- Array CGH (aCGH), Bone Marrow or Blood
- Microarray CGH, Bone Marrow or Blood
- Chromosomal Microarray Analysis, Bone Marrow or Blood
- Array for Neoplasia, Bone Marrow or Blood
- CMA, Hematologic Malignancy
- Cytogenomic Microarray, Neoplasia
- Cancer Cytogenomic Microarray, Bone Marrow or Blood
- SNP Array, Bone Marrow or Blood
- Cancer Array
Specimen transport should be arranged so that the specimen is received by MLabs the same day it is collected. Call for a STAT courier if necessary. Collect specimen in a lavender top or green top (sodium heparin) tube. Invert the tube several times to prevent clotting. Send the specimen intact at room temperature as soon as possible. DO NOT CENTRIFUGE. Include pertinent medical finding and diagnosis. Most insurance carriers require prior authorization for payment. Testing will not begin until insurance prior authorization is received, it is confirmed that prior authorization is not required, or the patient has agreed to pay out of pocket. A completed Michigan Medicine Request and Consent for Genetic Testing form is required and is available by calling 800-862-7284 or online: https://mlabs.umich.edu/sites/default/files/2020-01/file/pci-mmgl_infor….
Appropriate FISH testing on a separate sample will be performed at an additional charge to confirm, clarify, or further characterize the Cancer Cytogenomic Array results if necessary. By ordering this test the clinician acknowledges that additional reflex testing will be performed and billed at a separate additional charge if indicated. Also, by ordering this test the clinician acknowledges that informed consent has been obtained from the patient as required by applicable state or federal laws.