hotspot mutation
A genetic alteration occurring at a specific genomic location with high frequency across multiple patients, often representing key driver mutations with therapeutic implications.
Full Definition
Hotspot mutations are genetic alterations that occur repeatedly at the same nucleotide positions across different tumors and patients, indicating critical functional importance in cancer biology. These mutations typically affect amino acids crucial for protein function, such as kinase active sites or DNA-binding domains. Common examples include PIK3CA H1047R, KRAS G12C, and BRAF V600E mutations. Hotspot regions are prioritized in targeted gene panel designs because they represent the most clinically actionable alterations with established therapeutic relevance. The recurrent nature of these mutations suggests strong selective pressure and functional significance. Editors should recognize that hotspot status often influences variant interpretation and clinical decision-making, as these mutations typically have well-characterized functional and therapeutic implications.
Usage
Usage note: Often specified with gene and amino acid change (e.g., BRAF V600E hotspot); distinguish from broader driver mutation category.
In Context
- "The KRAS G12C hotspot mutation was detected at 45% variant allele frequency." — Molecular test result
- "Hotspot mutation analysis revealed a PIK3CA H1047R alteration associated with PI3K pathway activation." — Genomic profiling report