BOSTON AND CAMBRIDGE, Mass.Tumors are not factories for the mass production of identical cancer cells, but are, in reality, patchworks of cells with different patterns of gene mutations. In a new study, researchers at Dana-Farber Cancer Institute and the Broad Institute show, more fully than ever before, how these mutations shift and evolve over time in chronic lymphocytic leukemia (CLL) providing a strobe-like look at the genetic past, present, and future of CLL tumors.
Their report, which will be published online today by the journal Cell, suggests that evolution holds the key to understanding why CLL often recurs after treatment, and to the development of better therapies. The study helps explain why patients with a seemingly similar disease often don't derive the same benefit from therapy, why CLL recurs faster in some patients than others, and why therapy itself may speed the recurrence of the disease.
"One of the biggest challenges that patients with CLL and their physicians face is how to deal with relapse," said study co-senior author, Catherine Wu, MD, of Dana-Farber. "It's been clear for some time that tumors are collections of different subgroups of cells, each with a particular set of gene mutations, and that, over time, some of these subgroups become more prevalent and some less. So the tumor that you initially treat can be quite different, from a genetic standpoint, from the tumor that recurs later on."
For this study, Wu and her colleagues used next-generation gene-sequencing technology to chart changes in close to 100 samples of CLL tissue. "From there," Wu explained, "we began exploring how these different subgroups of cells influence the effectiveness of therapy. What can these subgroups tell us about how the cancer originated and developed, and how and how long it will respond to treatment before relapsing?"
Co-senior author Gad Getz, PhD, of the Broad Institute and Massachusetts General Hospital, a
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Dana-Farber Cancer Institute