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Study tracks leukemia's genetic evolution, may help predict disease course, tailor care
Date:2/14/2013

nd colleagues analyzed the genetic material in CLL tissue samples from 149 patients. Getz noted that the analysis was made possible due to the marriage of two tools his team recently developed. The first, a highly sensitive mutation calling method known as MuTect (concurrently published in Nature Biotechnology) can detect mutations present in a small fraction of cells. The second, ABSOLUTE (developed by a co-first author of this work, Scott L. Carter, PhD), uses the detected mutations as well as copy-number alterations to identify sub-populations within the cancer cells, and associates each mutation with the fraction of cancer cells that carried it.

"These tools opened a new window into the complexity of cancer and its evolution," said Getz. "This allowed us to ask which sub-populations of cancer cells increase or decrease with therapy and what happens when treating a patient that has a subset of cancer cells with additional cancer-driving mutations."

Rather than probing the entirety of the cancer cells' DNA, they focused just on the sections of DNA that hold code for making cell proteins. With technology capable of reading the genetic code letter by letter, they scoured the cells' DNA for mutations or spelling errors in specific genes. For 18 patients, they sampled CLL cells several years apart, enabling them to track changes in the cells' genetic makeup over time.

Their findings:

  • By taking genetic "snapshots" of CLL in many patients some newly diagnosed with the disease, some who had undergone lengthy treatment, some whose disease had recurred researchers were able to trace changes in the mix of subgroups of cells over time. This enabled them to reconstruct, in effect, a genetic biography of a patient's disease, identifying mutations that cropped up early in the disease, as well as those that came later.

  • Certain "driver" mutations named for their ability to spur cancer formation and growth tend to appear
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Contact: Teresa Herbert
teresa_herbert@dfci.harvard.edu
617-632-5653
Dana-Farber Cancer Institute
Source:Eurekalert  

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Study tracks leukemia's genetic evolution, may help predict disease course, tailor care
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