Fig. 4

Roles of extrachromosomal circular DNA with oncogene variation in therapeutic response. After the formation of extrachromosomal circular DNA, the amplified circular DNA elements are prone to pass on oncogene variations upon amplification, such as EGFRvIII and ALEM. In response to environmental changes, cancer cells might accordingly increase or decrease the copy number of circular DNA elements containing oncogene variations, leading to anticancer therapy resistance