Fluorescence in situ hybridization (FISH) detects specific DNA sequences in chromosomal spreads or interphase nuclei. In a patient with suspected BCR-ABL1 fusion (CML), dual-fusion FISH (D-FISH) is preferred over break-apart FISH. Why?
- A D-FISH uses DAPI counterstaining to directly visualize the Philadelphia chromosome as a smaller chromosome
- B D-FISH uses probes flanking both BCR and ABL1 loci; fusion of the two signals (yellow) confirms t(9;22); it directly shows the fusion event rather than merely break-apart of a locus, reducing false positives from deletions ✓
- C Break-apart FISH cannot detect CML because the BCR-ABL1 fusion does not separate on G-banding
- D D-FISH probes are labeled with radioactive isotopes for higher sensitivity than fluorescent break-apart probes
Explanation
Dual-fusion FISH (D-FISH) uses two probes: one labeled green (for ABL1) and one labeled red (for BCR). In CML with t(9;22)(q34;q11), both probes come into proximity on the Philadelphia chromosome, generating a yellow fusion signal. The pattern is 1 red + 1 green + 2 yellow (one fusion on Ph chromosome, one on der(9)). This directly confirms the translocation. Break-apart FISH is preferred for loci with multiple partner genes (e.g., ALK, MYC) when the partner is variable — it shows split of a single locus. For BCR-ABL1 where the specific partner is known, D-FISH is more specific because it requires BOTH probes to co-localize.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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