Oncogenes out of context: Cancer genes break free from the regulatory constraints of chromosomes.

Human DNA is organized into 23 pairs of chromosomes, which provide the templates for the proteins that make up the body. Occasionally, chromosomes can break or mutate by mistake. This creates changes in molecular networks and can alter cell functions, driving abnormal cell growth in cancer. A dramatic type of genetic change in cancer is when extra copies of DNA are formed outside chromosomes. These extra DNA copies, or extrachromosomal DNA (ecDNA), were originally discovered in the 1960s in pediatric tumors (1) and called "double minutes" because they often appear as paired dots on chromosome spreads. In the following decades, they were found in many types of cancer and shown to carry oncogenes (2), thus dysregulating growth signals in cells. ecDNAs appear to have distinct properties from chromosomes. For example, they form circular rather than linear DNA structures (3). They also lack centromeres and therefore divide unevenly during cell division (4, 5). However, how ecDNAs affect oncogene activity and the evolutionary dynamics of cancer cells has been poorly understood. [ABSTRACT FROM AUTHOR]