Extrachromosomal oncogene amplification in tumour pathogenesis and evolution.
Nat Rev Cancer 2019 Mar 14 [Epub ahead of print]
CA190121,CA034196,Musella Foundation, B*CURED Foundation
Recent reports have demonstrated that oncogene amplification on extrachromosomal DNA (ecDNA) is a frequent event in cancer, providing new momentum to explore a phenomenon first discovered several decades ago. The direct consequence of ecDNA gains in these cases is an increase in DNA copy number of the oncogenes residing on the extrachromosomal element. A secondary effect, perhaps even more important, is that the unequal segregation of ecDNA from a parental tumour cell to offspring cells rapidly increases tumour heterogeneity, thus providing the tumour with an additional array of responses to microenvironment-induced and therapy-induced stress factors and perhaps providing an evolutionary advantage. This Perspectives article discusses the current knowledge and potential implications of oncogene amplification on ecDNA in cancer.
Verhaak, Roel G W; Bafna, Vineet; and Mischel, Paul S, "Extrachromosomal oncogene amplification in tumour pathogenesis and evolution." (2019). Faculty Research Ahead of Print. 154.