loss of heterozygosity
Also written as: LOH — Loss of Heterozygosity
The loss of one functional copy of a gene in cancer cells, often affecting tumor suppressor genes and following Knudson's two-hit hypothesis for cancer development.
Full Definition
Loss of heterozygosity (LOH) occurs when cancer cells lose one of two allelic copies of a gene, typically involving tumor suppressor genes where both copies must be inactivated for cancer development. This phenomenon follows Knudson's two-hit hypothesis, where an inherited or acquired mutation inactivates one allele (first hit) and LOH eliminates the remaining functional copy (second hit). LOH can result from chromosomal deletion, mitotic recombination, or chromosome loss followed by duplication. Common examples include LOH at BRCA1/2 loci in hereditary breast cancers and p53 LOH in various tumor types. Detection of LOH can indicate tumor suppressor gene involvement and may have therapeutic implications, particularly for synthetic lethal approaches. Modern sequencing platforms can detect LOH through analysis of variant allele frequencies in heterozygous germline variants.
Usage
Usage note: Commonly abbreviated as LOH; distinguish from homozygous deletion which involves loss of both copies.
In Context
- "Loss of heterozygosity analysis revealed 17q LOH encompassing the BRCA1 locus." — Genomic analysis report
- "The tumor showed loss of heterozygosity for multiple tumor suppressor gene regions." — Cytogenetic analysis summary