The pan-tumor landscape of gene amplifications and copy number amplification ratio for established and emerging clinical targets - PubMed
2 hours ago
- #gene amplification
- #copy number variation
- #precision medicine
- Gene copy number (CN) amplifications and protein overexpression are common drug targets.
- A novel method called AmpRatio was developed for CN quantitation by dividing gene CN by sample ploidy.
- Amplifications were found in 38.6% of pan-tumor tissue samples, with MYC, 11q13, ERBB2, and CCNE1 being the most frequent.
- ERBB2 AmpRatio showed high agreement with HER2 positivity by IHC/FISH in gastroesophageal (90%) and breast (95%) cancers.
- ERBB2 AmpRatio significantly stratified outcomes in patients treated with anti-HER2 therapies.
- High concordance (88% sensitivity) of amplification detection was observed in liquid biopsy vs tissue when ctDNA tumor fraction was ≥20%.
- AmpRatio varies across genes and tumor types, suggesting its utility alongside IHC for clinical decision-making.
- Harmonized methods for CN quantification are needed for optimal patient selection with therapies targeting amplifications/overexpression.