Detection and characterization of clonal copy number imbalance and loss of heterozygosity associated with hematologic neoplasms
Assisting in the diagnosis and classification of certain hematologic neoplasms
Evaluating the prognosis for patients with certain hematologic neoplasms
DNA extraction is always performed on the specimen prior to hybridization to the microarray. An unstimulated cell culture will be set up on all specimens with adequate volume and held pending additional testing. If additional testing is requested, such as karyotype analysis or fluorescence in situ hybridization, it will be performed at an additional charge.
The following algorithms are available:
Chromosomal Microarray (CMA) Using Applied Biosystems (Affymetrix) Cytoscan HD
aCGH
Array CGH
Array Comparative Genomic Hybridization
Oligonucleotide Array
Oligo Array
Single Nucleotide Polymorphism (SNP) Array
Whole Genome Array
Microarray
CytoScan
Hematology Array
Hematologic Array
Heme Array
Loss of Heterozygosity (LOH)
Copy Neutral Loss of Heterozygosity (cnLOH)
DNA extraction is always performed on the specimen prior to hybridization to the microarray. An unstimulated cell culture will be set up on all specimens with adequate volume and held pending additional testing. If additional testing is requested, such as karyotype analysis or fluorescence in situ hybridization, it will be performed at an additional charge.
The following algorithms are available:
Varies
This test is not appropriate for detecting constitutional/congenital copy number changes or regions of excessive homozygosity. If this test is ordered with a reason for testing indicating a constitutional/congenital disorder, the test will be canceled and CMACB / Chromosomal Microarray, Congenital, Blood will be performed as the appropriate test.
1. A reason for testing must be provided for testing to be performed.
2. A pathology report should accompany the specimen. If this information is not available at the time of order, submit as soon as possible for appropriateness of testing and to aid in interpretation of results.
| Question ID | Description | Answers |
|---|---|---|
| CG902 | Reason for Referral | |
| CG903 | Specimen |
Submit only 1 of the following specimens:
Specimen Type: Bone marrow
Container/Tube:
Preferred: Green top (sodium heparin)
Acceptable: Lavender top (EDTA)
Specimen Volume: 1-2 mL
Collection Instructions:
1. Invert several times to mix bone marrow.
2. Send bone marrow specimen in original tube. Do not aliquot.
Specimen Type: Whole blood
Container/Tube:
Preferred: Green top (sodium heparin)
Acceptable: Lavender top (EDTA)
Specimen Volume: 7-10 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.
Blood: 2 mL
Bone marrow: 1 mL
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Refrigerated | |||
Detection and characterization of clonal copy number imbalance and loss of heterozygosity associated with hematologic neoplasms
Assisting in the diagnosis and classification of certain hematologic neoplasms
Evaluating the prognosis for patients with certain hematologic neoplasms
DNA extraction is always performed on the specimen prior to hybridization to the microarray. An unstimulated cell culture will be set up on all specimens with adequate volume and held pending additional testing. If additional testing is requested, such as karyotype analysis or fluorescence in situ hybridization, it will be performed at an additional charge.
The following algorithms are available:
The importance of identifying chromosome abnormalities in hematologic disorders is well established and often provides important diagnostic, prognostic, and therapeutic information critical to proper patient management. Although many chromosomal abnormalities are large enough to be detected with conventional chromosome analysis, many others are below its limits of resolution, and conventional chromosome analysis does not detect copy-neutral loss of heterozygosity.
Chromosomal microarray (CMA) improves the diagnostic yield to identify genetic changes that are not detected by conventional chromosome analysis or fluorescence in situ hybridization (FISH) studies. CMA utilizes greater than 1.9 million copy number probes and approximately 750,000 single nucleotide polymorphism probes to detect copy number changes and regions of copy-neutral loss of heterozygosity.
CMA analysis is appropriate to identify gain or loss of chromosome material throughout the genome at a resolution of 30 to 60 kilobases. CMA can do the following:
-Define the size, precise breakpoints, and gene content of copy number changes to demonstrate the complexity of abnormalities
-Characterize unidentified chromosome material, marker chromosomes, and DNA amplification detected by conventional chromosome and FISH studies
-Determine if apparently balanced chromosome rearrangements identified by conventional chromosome studies have cryptic imbalances
-Assess regions of copy-neutral loss of heterozygosity, which is common in neoplasia and often masks homozygous mutations involving tumor suppressor genes
The limit of detection is dependent on size of the abnormality, type of abnormality (deletion or duplication) and DNA quality. When a deletion or duplication exceeds the reporting limits, mosaicism can confidently be detected as low as 25% and may be lower if the abnormality is large and DNA quality is good.
An interpretive report will be provided.
The interpretive report describes copy number changes and any loss of heterozygosity that may be associated with the neoplastic process. Abnormal clones with subclonal cytogenetic evolution will be discussed if identified.
The continual discovery of novel copy number variation and published clinical reports means that the interpretation of any given copy number change may evolve with increased scientific understanding.
Although the presence of a clonal abnormality usually indicates a neoplasia, in some situations it may reflect a benign or constitutional genetic change. If a genetic change is identified that is likely constitutional and clearly pathogenic (eg, XYY), consultation with a Clinical Geneticist may be suggested.
The absence of an abnormal clone may be the result of specimen collection from a site that is not involved in the neoplasm or may indicate that the disorder is caused by a point mutation that is not detectable by chromosomal microarray (CMA).
CMA, fluorescence in situ hybridization (FISH), and conventional cytogenetics are to some extent complementary methods. In some instances, additional FISH or conventional cytogenetic studies will be recommended to clarify interpretive uncertainties.
This test is not approved by the US Food and Drug Administration, and it is best used as an adjunct to existing clinical and pathologic information.
This test does not detect balanced chromosome rearrangements such as reciprocal translocations, inversions, or balanced insertions.
This test does not detect point variants, small deletions or insertions below the resolution of the assay, or other types of variants such as epigenetic changes.
Low level abnormal clones may not be detected by this test; as such it is not recommended for minimal residual disease.
This test does not identify tetraploidy, although in concert with other studies tetraploidy can be inferred.
The results of this test may reveal incidental findings not related to the original reason for testing.
The chromosomal microarray was validated on the Affymetrix CytoScan HD platform in a blinded study of 30 specimens from a variety of hematologic disorders. Results were correlated to previous conventional karyotype and fluorescence in situ hybridization analysis.
1. Cooley L, Lebo M, Li M, et al: American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders. Genet Med. 2013 Jun;15(6):484-494
2. Dougherty M, Wilmoth D, Tooke L, et al: Implementation of high resolution single nucleotide polymorphism array analysis as a clinical test for patients with hematologic malignancies. Cancer Genetics. 2011 Jan;204(1):26-38
3. Schwartz, S: Clinical Utility of Single Nucleotide Polymorphism Arrays. Clin Lab Med. 2011 Dec;31(4):581-594
4. Braggio E, Kay N, VanWier S, et al: Longitudinal genome-wide analysis of patients with chronic lymphocytic leukemia reveals complex evolution of clonal architecture at disease progression and at the time of relapse. Leukemia. 2012 Jul;26(7):1698-1701
DNA extracted from the patient's bone marrow or peripheral blood is labeled and hybridized to the microarray. Following hybridization, the microarray is scanned, and the intensity of signals is measured and compared to a reference data set. These data are used to determine copy number changes and regions with loss of heterozygosity. Chromosomal microarray data alone do not provide information about the structural nature of an imbalance. Thus, it may be of benefit to utilize fluorescence in situ hybridization or additional techniques to further characterize a patient sample.(Unpublished Mayo method)
Monday through Friday
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
81277
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| CMAH | Chromosomal Microarray, Hematologic | 94087-4 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 54721 | Result Summary | 50397-9 |
| 54722 | Result | 62356-1 |
| 54723 | Nomenclature | 62378-5 |
| 54724 | Interpretation | 69965-2 |
| CG902 | Reason for Referral | 42349-1 |
| CG903 | Specimen | 31208-2 |
| 54725 | Source | 31208-2 |
| 54726 | Method | 85069-3 |
| 53423 | Additional Information | 48767-8 |
| 54727 | Released By | 18771-6 |