Tumors Evolve Rapidly In A Childhood Cancer, Leaving Fewer Obvious Treatment Targets
However, while the researchers confirmed that roughly 10 percent of the study's neuroblastoma patients had ALK mutations, and found that a handful of other gene mutations each accounted for percentages in the single digits, there were relatively few recurrent mutations in somatic (non-germline) cells. "The relative paucity of recurrent mutations challenges the concept that druggable targets can be defined in each patient by DNA sequencing alone," wrote the authors.
In the absence of frequently altered oncogenes that drive high-risk neuroblastomas, the authors concluded that most such cases may result from other changes: rare germline mutations, copy number variations and epigenetic modifications during tumor evolution.
"Personalized medicine is more complex than we had hoped," said Maris. "While there are successes such as those in treating patients whose tumors harbor ALK mutations, this study implies that we must think very differently about how we'll use genomics to define treatment." Maris added that neuroblastoma researchers may need to turn to functional genomics, learning which tumors will or won't respond to treatments, as well as going beyond a static picture of a cancer cell with fixed genetic contents, to devising interventions to deal with dynamic tumor cells that evolve during nervous system development.
Co-corresponding authors with Maris are Matthew Meyerson, M.D., Ph.D., of the Broad Institute, Harvard Medical School and Dana-Farber Cancer Institute, and Marco A. Marra, Ph.D., of the University of British Columbia. In addition to his position at Children's Hospital, Maris also is on the faculty of the Perelman School of Medicine at the University of Pennsylvania.Support for this study came from the National Institutes of Health (grants CA98543, CA98413, MD004418, CA124709, CA060104, and HG003067), the Canada Research Chair in Genome Science, the Giulio D'Angio Endowed Chair, the Alex's Lemonade Stand Foundation, the Arms Open Wide Foundation, and the Cookies for Kids Foundation.
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