An oncology chromosomal microarray (CMA) looks for acquired, clonal segmental or whole chromosome arm abnormalities in the tumor genome. Oncology CMA may also be useful for detecting masked hypodiploid karyotypes. Large spans of Loss of Heterozygosity (LOH) are also detectable.

Indications

ACMG recommends CMA be considered as a complementary method to chromosome analysis and/or FISH for detection of chromosomal copy number changes in neoplastic disorders.

Limitations

The CMA platform does not reliably detect copy number changes in neoplastic cells when tumor content is <40% of the test specimen. CNVs that are smaller than the resolution of the array may not be detected or reported. Segmental copy number aberrations are defined as genomic regions of ≥1 Mb in size but less than a whole chromosome arm, or Loss of Heterozygosity (LOH) ≥5 Mb.

This assay does not detect balanced structural rearrangements, copy number changes in genomic regions not represented on the microarray, deletions and duplications with limited probe coverage, gene expansions, or single nucleotide variants/polymorphisms. This assay should not be interpreted as a complete analysis of the genome to rule out germline abnormalities or a complete analysis of the tumor genome. In cases where a clinically significant abnormality is suggestive of a germline abnormality associated with a genetic disorder, the laboratory may contact the ordering provider to suggest additional germline testing. 

Methods

Chromosomal microarray (CMA) was performed on extracted DNA and processed on the Illumina® Infinium Global Diversity bead array. Using SNP (single nucleotide polymorphism) probes, the microarray detects copy number losses and gains with a resolution of approximately 5 kb across the genome. These probes also enable detection of regions of copy neutral loss of heterozygosity (LOH); genomic regions with loss of allelic diversity without a corresponding change in copy number. Patient DNA is extracted, amplified, enzymatically fragmented, and hybridized to the probes on the array. The array is washed, scanned on Illumina’s iScan Platform, and the data is analyzed and interpreted using VIA software (Bionano Inc.).  

If LOH is identified in a region of interest in the presence of normal copy number and is smaller than a whole chromosome arm, analysis of a germline specimen may be performed to determine if the segmental LOH is somatic or germline (PMIDs: 23619274, 31138931). Data analysis is based on the GRCh37/hg19 assembly and interpretation is based on available resources including information from the Database of Genomic Variants, scientific literature, and an internal copy number variation database.  

Turn Around Time

7-14 days, up to 21 for FFPE specimens

The targeted oncology chromosomal microarray (CMA) looks for acquired, clonal segmental or whole chromosome arm aberrations in regions of the genome where gains and/or losses are known to contribute to the etiology of various cancers. Large spans of Loss of Heterozygosity (LOH) are also detectable.

Cancer Types Tested

• Wilm’s tumor: Special attention to somatic clonal segmental copy number losses or loss of heterozygostity (LOH) in the chromosome regions 1p, 11p15, 16q, or 17p, and copy number gain in the chromosome region 1q (PMIDs: 27400937, 16129848, 25313908, 21189373).
• Neuroblastoma: Specially attention to somatic segmental clonal copy number losses or loss of heterozygostity (LOH) in the chromosome regions 1p, 3p, or 11q, copy number gains of 1q, 2p, or 17q, or amplification of MYCN (2p24.3) (PMIDs: 19171713, 26304901).
• Other tumors as requested. Please contact CGL for further information at 303-724-5701.

Segmental copy number aberrations are defined as genomic regions of >1 Mb in size but less than a whole chromosome arm, or Loss of Heterozygosity (LOH) >5 Mb.

Limitations

This evaluation is not intended to be an analysis of the entire genome. Information on other chromosome regions is reported if possibly clinically significant or for completeness. Those seeking a copy number analysis across the entire genome should order a standard Chromosomal Microarray.

The CMA platform does not reliably detect copy number changes in neoplastic cells when tumor content is <40% of the test specimen. CNVs that are smaller than the resolution of the array may not be detected or reported. Segmental copy number aberrations are defined as genomic regions of ≥1 Mb in size but less than a whole chromosome arm, or Loss of Heterozygosity (LOH) ≥5 Mb.

This assay does not detect balanced structural rearrangements, copy number changes in genomic regions not represented on the microarray, deletions and duplications with limited probe coverage, gene expansions, or single nucleotide variants/polymorphisms. This assay should not be interpreted as a complete analysis of the genome to rule out germline abnormalities or a complete analysis of the tumor genome. In cases where a clinically significant abnormality is suggestive of a germline abnormality associated with a genetic disorder, the laboratory may contact the ordering provider to suggest additional germline testing. 

Methods

Chromosomal microarray (CMA) was performed on extracted DNA and processed on the Illumina® Infinium Global Diversity bead array. Using SNP (single nucleotide polymorphism) probes, the microarray detects copy number losses and gains with a resolution of approximately 5 kb across the genome. These probes also enable detection of regions of copy neutral loss of heterozygosity (LOH); genomic regions with loss of allelic diversity without a corresponding change in copy number. Patient DNA is extracted, amplified, enzymatically fragmented, and hybridized to the probes on the array. The array is washed, scanned on Illumina’s iScan Platform, and the data is analyzed and interpreted using VIA software (Bionano Inc.).  

If LOH is identified in a region of interest in the presence of normal copy number and is smaller than a whole chromosome arm, analysis of a germline specimen may be performed to determine if the segmental LOH is somatic or germline (PMIDs: 23619274, 31138931). Data analysis is based on the GRCh37/hg19 assembly and interpretation is based on available resources including information from the Database of Genomic Variants, scientific literature, and an internal copy number variation database.  

Turn Around Time

7-14 days, up to 21 for FFPE specimens

Fluorescence in situ hybridization (FISH) detects chromosome aneuploidy, specific genomic copy number changes such as deletions and duplications below the level visible on chromosome analysis, and specific fusions and rearrangements. Some copy number changes and rearrangements are associated with various forms of neoplasms and tumors. Robust oncology analysis often pairs Chromosome Analysis with FISH testing.

Please see the Oncology FISH Panels and Individual Probe List below for a comprehensive view of all the probes and tests we provide.

Indications

• Suspicion of acquired clonal chromosome abnormalities associated with tumors, lymphomas, and hematological neoplasms
  

Limitations

As FISH probes bind to specific loci, copy number changes, rearrangements, or other chromosome abnormalities not involving the binding site will not be evaluated by this assay.

Turn Around Time

3-14 days

Donor chimerism FISH is performed on patients who have received a transplant from an opposite sex donor to determine the proportion of recipient (patient) and donor cells.

Indications

• Recipient (patient) and donor of opposite sex

Probes: X cen/Yqh

Turn Around Time

1-7 days