In Science this week, a University of California, San Francisco-led research team presents the genomes of 23 low-grade gliomas, making note of the recurrences of these tumors, in order to determine whether genetics plays a role in the resistance of some cancers to treatment. Whole-exome analysis showed that recurrent tumors did, in fact, have a distinct set of genetic mutations compared with their original tumors. Notably, tumors from six of 10 patients treated with a chemotherapeutic that damages DNA followed "an alternative evolutionary path to high-grade glioma." At recurrence, they were hypermutated and harbored driver mutations that made them especially aggressive.
Also in Science, three New York University School of Medicine researchers discuss the importance of the three-dimensional organization of the genome in both legitimate and illegitimate DNA recombination. They cite studies showing the importance of nuclear proximity in chromosomal translocations resulting from DNA double-strand breaks, as well as homologous recombination, and how chromosome mobility impacts the repair of double-strand breaks. " In the future, it will be important to identify the factors that promote chromosome movement by tracking the activities of wild-type and mutant repair proteins and remodeling factors over a period of time after the introduction of a break," they add. "It will also be necessary to generate systems that better define the contribution of transcription, replication, accessibility, and so on in creating abnormal DNA rearrangements. This is particularly relevant for the design of cancer therapies that do not promote translocations, which further contribute to oncogenic relapse."