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A Bad Shuffle

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Researchers at Children's Hospital Boston and at Harvard's Immune Disease Institute have created a method to identify possible break points in the genome where chromosomes are susceptible to break and recombine, according to a Children's Hospital press release. A deep understanding of where and when chromosomes are likely to break could advance researchers' knowledge of cancer genomics and help guide the development of gene therapy-based treatments for a number of diseases, the press release adds. When chromosomes break, they are sometimes rearranged, and these translocations can sometimes form new fusion genes that can lead to cancer. The study, published in Cell, elucidates the mechanisms behind this chromosomal shuffling, the researchers say. The team's mapping method for the "translocatome" — what they're calling the genome-wide effects of these translocations — is called "high-throughput genome-wide translocation sequencing," the hospital says, and "is based on the action of DNA-cutting enzymes such as I-SceI, a general type of enzyme that is also under scrutiny as a possible gene therapy tool." The researchers found that the broken pieces of the chromosome tend to fuse near the beginning of genes with high frequency, and that the fragments tend to rearrange themselves within the same chromosome instead of sharing pieces across different chromosomes. "This greater understanding of where and the rules by which translocations occur could lead to a new way of thinking about how particular genes and translocations contribute to cancer," the press release says. "For instance, HTGTS could help scientists figure out which oncogenes might contribute to different tumors by showing which have a high potential for containing translocation sites in tumor progenitors." This could be particularly useful for childhood cancers like leukemia or lymphoma, in which translocations tend to be more common.

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