tumor suppressor haploinsufficiency
Pronunciation: HAP-low-in-suh-FISH-en-see
A condition where loss of one functional copy of a tumor suppressor gene reduces cellular growth control below the threshold needed for normal function.
Full Definition
Tumor suppressor haploinsufficiency occurs when a single functional copy of a tumor suppressor gene is insufficient to maintain normal cellular growth control, even without complete loss of the second allele. This mechanism differs from the classical 'two-hit hypothesis' where both copies must be inactivated for cancer predisposition. Haploinsufficient tumor suppressors include genes like TP53, PTEN, and NF1, where heterozygous loss can contribute to tumorigenesis. In cancer genomics reporting, recognition of haploinsufficiency is crucial for interpreting the clinical significance of heterozygous deletions and nonsense mutations in these genes. This concept has important implications for cancer risk assessment and therapeutic targeting.
Usage
Usage note: Emphasize distinction from classical two-hit model; important for variant interpretation.
In Context
- "The heterozygous PTEN deletion was classified as pathogenic due to tumor suppressor haploinsufficiency." — Genetic counseling report
- "Evidence for haploinsufficiency was supported by the dosage-sensitive nature of this tumor suppressor." — Molecular pathology assessment