The Curious DNA Circles that Make Treating Cancer so Hard

To the untrained eye, the tiny spots in the tumor cell wouldn’t look like much. In fact, other scientists had noticed them in cancer before but had generally dismissed them as a mere curiosity. But to Paul Mischel, the fuzzy dots he saw under the microscope offered a tantalizing explanation for why some cancers are so hard to treat.

Mischel first noticed the spots almost a decade ago while studying tumors that had gene amplifications, a mutation characterized by multiple copies of a gene linked to cancer growth. Those extra copies cause cells to churn out proteins that encourage the tumor to keep expanding. Scientists had assumed the copies were stacked back to back amid the other genes on our X-shaped chromosomes, as if the same page had been accidentally printed over and over in the middle of a book.

Mischel stained the gene amplifications red and the cancer cell’s chromosomes blue. If conventional wisdom held, his microscope would reveal a glob of red dotting one of the blue chromosomes. Instead, the physician-scientist saw dozens of small red dots scattered outside the chromosomes. It was as if someone had photocopied a page from the book and then tossed the copies in the air.