Table 1.
Comparison of CBA, FISH, and CMA for the Detection of Genomic Changes in CLL
| Cytogenetic test | Advantage (strength) of the test | Disadvantage (weakness) of the test |
|---|---|---|
| CBA | Genome-wide scan Single cell analysis Detection of balanced chromosome rearrangements (ie, translocations, inversions) Sensitivity is circa 10% to 15% in routine analysis: 2 (loss) or 3 (gain) aberrant metaphases found in 20 analyzed cells Detection of clonal evolution Discovery of novel abnormalities (and complex karyotype) |
Requires culturing of cells with B-cell mitogen (eg, IL2 + CpG) to increase sensitivity Resolution limit is 10–20 Mb Exact definition of rearrangements may not be evident by banding-analysis alone Cannot detect regions of homozygosity (CN-LOH) Analysis is laborious and slow (1 case at a time) |
| FISH | Resolution is circa 150–900 kb, depending on probe-size Sensitivity for detection of low level clones is around 3%–5% (usually 100–200 interphase nuclei scored) Does not require cultured cells Batch cases |
Detects only abnormalities where the probe was designed for Multiple FISH probes are required to look at diverse abnormalities (routinely in CLL a 4–5 probe panel) Clonal evolution may be overlooked Cannot detect regions of homozygosity (CN-LOH) or genomic instability (chromothrypsis) |
| CMA | Whole genome scan Resolution is 50 kb or less (depending on platform design) Discovery of novel abnormalities (and genomic complexity) Detection of regions of homozygosity (CN-LOH) if SNP-based platform Significantly automated (batch cases) Does not require cultured cells Discovery of novel unbalanced abnormalities with exact definition of the regions (and genes) involved (within the limit of resolution) Detection of (submicroscopic) regions with genomic instability/chromothripsis |
Cannot detect balanced chromosome rearrangements Detection of multiple clones is feasible but not evident Sensitivity is 10%–20% (platform-dependent) B-cell enrichment may be required if tumor burden is low |