Table 3 Summary of LOH – what is it good for?
Hypothesis | Mechanism | Plausibility | Frequency | Impact | LOH type |
|---|---|---|---|---|---|
Classic two-hit hypothesis | High frequency biallelic genetic inactivation of TSG via mutation and LOH or homozygous deletion | Strong | Rare | High | More CNN-LOH |
Modified two-hit hypothesis | Reduction to homozygosity of predisposition alleles | Low | Rare | Low | Unknown |
Epigenetic two-hit hypothesis | Biallelic inactivation through methylation and LOH | Moderate | Unknown | Moderate | More CNN-LOH |
Haplo-insufficiency | Single copy gene disruption through copy number loss | Strong | Common | Moderate | CNL-LOH |
Multi-gene biallelic inactivation | Low frequency gene disruption through all of the above mechanisms | Strong | Common | Unknown | Either |