coamplification

Coamplification refers to the simultaneous increase in copy number of two or more genomic loci, typically within the same chromosomal region, leading to the overexpression of multiple genes. It is often observed in cancer genomes and is a form of focal amplification that can affect gene regulation, signaling pathways, and cellular phenotypes.

Coamplification can arise through mechanisms that create or maintain amplified DNA, including focal high-level copy number gains, extrachromosomal DNA or double minutes, and chromosomal rearrangements such as breakage-fusion-bridge cycles. These processes can produce complex amplicons containing several neighboring genes, sometimes extending beyond a single gene to include distal partners.

The biological and clinical implications of coamplification are context dependent. When multiple oncogenes are coamplified, tumors may gain redundant or synergistic growth signals, potentially influencing aggressiveness and response to therapy. Coamplified genes can also complicate the identification of the true driver gene(s) responsible for a growth advantage, and may contribute to mechanisms of drug resistance if several targets are amplified simultaneously.

Detection of coamplification relies on genome-wide copy-number analysis and targeted locus assessment. Methods include comparative genomic hybridization, SNP arrays, and next-generation sequencing with read-depth or allele-imbalance analysis, complemented by fluorescence in situ hybridization to visualize amplified loci. EcDNA-based amplifications can be identified through imaging and specialized sequencing approaches.

In research and clinical settings, recognizing coamplification helps map driver regions, interpret gene-expression data, and inform potential combination therapeutic strategies, while acknowledging that not all coamplified genes are functionally consequential.