|
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
|
