Targeting multiple genetic aberrations in isolated tumor cells by spectral fluorescence in situ hybridization

Purpose: Tumorigenesis is characterized by the stepwise accumulation of multiple genetic changes that modify specific growth controls and cell survival. Conventional fluorescence in situ hybridization (FISH) assays reliably target one to three probes in a single hybridization. Simultaneous detection of more than three chromosomal or gene targets should increase the overall power of molecular cytogenetics by permitting detection of multiple genetic aberrations at the single cell level. Method: Spectral FISH (S-FISH) is an innovative molecular cytogenetic approach that can target many specific chromosomal aberrations in interphase and metaphase cells in a single hybridization, using combinatorial fluorescence and digital imaging microscopy. Results: S-FISH is a reliable means to identify disease-specific aberrations at the DNA level in individual tumor cells in hematopoietic disorders and malignant melanoma. Conclusion: S-FISH is a sensitive assay for the diagnosis and monitoring of disease-specific or patient-specific genetic aberrations, with significant clinical application in oncology for early detection of new or re-emerging abnormal clones, allowing for earlier therapeutic intervention.