Cancer May Be Driven by DNA Outside of Chromosomes

In the last decade, researchers have come to realize that tumors harbor bits of extrachromosomal DNA that can drive malignancy.

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In the spring of 2012, my colleagues and I began to notice something strange in tumor cells from patients with glioblastoma, a highly aggressive form of brain cancer, who were coming into our clinic at the University of California, Los Angeles. From genomic sequencing of their tumors, we knew they displayed amplification of a specific growth-promoting oncogene. Despite being treated with drugs designed to target this gene, the patients were not getting better, and when we interrogated the genomes of their cancers after the tumors were surgically removed following treatment, we saw that they had changed. The tumors had dramatically reduced the number of copies of the targeted epidermal growth factor receptor (EGFR) gene, presumably giving them an advantage to escape the drugs, and they had evolved these genetic differences at a rate that seemed to make no sense—within just one to two weeks.

Normally, ...

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  • Paul Mischel

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