One of the first things a cancer cell does is move around some of its genes, Meaburn and Misteli show.
Cells rearrange their DNA during certain diseases. In neurons from people with epilepsy, for instance, the X chromosome tends to be closer to the middle of the nucleus than in neurons from nonepileptics. Researchers have also observed chromosomal relocation in the few cancers they have examined. However, these observations involved late-stage disease, and no one knew what happened early in tumor development.
Meaburn and Misteli scrutinized mammary cells that they had coaxed to grow abnormally. When the researchers pinpointed 11 genes, they found that four—including the antiapoptotic gene BCL2—were in different positions in the cancer cells than in normal cells. Three of the genes were closer to the edge of the nucleus in the tumor cells, and one was closer to the center.
Some studies suggest that active genes tend to shift into the interior of the nucleus, whereas inactive genes are marginalized. But the team determined that the location of a particular gene in the nucleus didn't depend on its expression level. For example, activity of the gene for the extracellular matrix protein MMP1 shot up in the cancerous cells, but the gene remained in place. The researchers conclude that early in tumor formation, cancer cells reposition certain genes. Why the cells go to the trouble is a mystery, but the discovery might lead to new diagnostic tests.