Clinical Information

The importance of identifying chromosome abnormalities in malignant neoplasms 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 copy number probes and single nucleotide polymorphism probes to detect copy number changes and regions of copy-neutral loss of heterozygosity.

Chromosomal microarray analysis is appropriate to identify gain or loss of chromosome material throughout the genome at a resolution of 50 to 100 kilobases. CMA can:

-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.