Compared with their healthy cousins, cancer cells are a chaotic mess, often having extra chromosomes, abnormal shapes, and other odd attributes. Now scientists have discovered a strange feature that appears to be unique to cancer cells: long stretches of repetitive RNA, known as satellites. Preliminary research suggests that the satellites appear early in the development of cancer, a finding that may ultimately aid early detection.
“It’s a very interesting and provocative finding,” says Stuart Orkin, chairman of pediatric oncology at the Dana-Farber Cancer Institute, who was not involved in the research. “It suggests wholesale changes in gene expression in cancer cells that was previously unrecognized. It hints at how chromatin [the mass of DNA and proteins that make up chromosomes] and gene expression in cancer cells are deranged in a global fashion.”
David Ting, Daniel Haber, and collaborators at Massachusetts General Hospital discovered the markers by accident while Ting was studying RNA from tumor cells. The DNA that codes for genes is normally transcribed into RNA, which is then translated into proteins. Ting was puzzled by the appearance of RNA molecules whose sequence didn’t correspond to genes. He found that the sequences corresponded instead to satellites, stretches of repetitive DNA that are transcribed into RNA but never translated into proteins.
“We were surprised to find [the satellites] are expressed in abundant amounts in tumor tissue compared to normal tissue,” says Ting. Follow-up testing in both mouse and human cancer tissue revealed high levels of satellites in different types of tumors, including lung, kidney, ovarian, prostate, and pancreatic cancers.
“This is a fascinating finding because there is no precedent for finding a single class of [DNA] that is uniformly overexpressed in different types of cancer,” says Bert Vogelstein, professor of oncology and pathology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University. “It appears to be true in virtually every cancer they looked at.”
While scientists have known about the existence of satellite repeats in the genome for years—they make up about five percent of the genome—the role they play in healthy cells is still unclear. “For a long time, people have ignored it, thinking it was residual DNA,” says Ting. In fact, most software used to analyze DNA sequences is designed to eliminate these stretches from their analysis, he says.