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Gene pairs are tied to cancer spread

Medicine@Yale, 2019 - June July


Cancer is most deadly when it metastasizes, or spreads. While metastasis might result from malfunctions of single genes, interactions among multiple genes may also be the cause, complicating metastasis genetics. As reported April 8 in Nature Methods, Sidi Chen, PhD, assistant professor of genetics, has developed an approach designed to sort out which gene pairs most drive cancer’s spread.

Using the gene-editing technique CRISPR, Chen and colleagues knocked out 325 pairs of genes individually suspected of promoting metastasis from lung cancer cells. Next, with a subcutaneous injection, they transferred the cancer cells, which carried genetic barcodes indicating which genes had been knocked out, into immunodeficient mice. Six weeks later, the researchers removed both the primary tumors from under the skin and those that had metastasized to the lungs.

Through the barcodes, they determined which gene-knockout combinations were more prevalent in the lung tumors than in primary tumors and, therefore, which combinations had likely promoted metastasis. In addition to helping scientists understand cancer genetics, this approach could help researchers probe gene interactions in other contexts, the authors write.