Scientists have identified genetic clues to how a tumor spreads throughout the body. Understanding the genetic aberrations that enable the metastasis of cancers could help scientists design better prognostic tests and more effective treatments.

In the research, the scientists compared the genome sequence of a breast cancer patient with that of both her primary tumor and cancer cells that had spread to her brain. It is just one of two published papers comparing the genomic differences between a primary and metastatic tumor from the same patient, a challenging endeavor but one that allows scientists to track the cancer’s evolution. “A patient’s tumor is a living thing changing all the time,” says Matthew Ellis, an oncologist and scientist at Washington University, in St. Louis, and one of the study’s authors. “We’ve never been able to track that completely.”

Cancer results when healthy cells acquire a combination of genetic mutations that allow them to grow out of control. Scientists have identified a number of mutations that increase the risk of cancer, as well as predict its prognosis and its likelihood of responding to certain treatments. But much less is known about the genetic mistakes that enable tumor progression, especially metastasis. The new research, reported Wednesday in the journal Nature, “emphasizes that you can gain a lot from looking at the evolution of a cancer over time,” says Sam Aparicio, Canada Research Chair in molecular oncology, who was not involved in the study.

The researchers used sequencing technology from Illumina, a genomics company in San Diego, to analyze DNA from the patient’s healthy cells, from the primary tumor prior to treatment, and from the brain metastasis. They found 48 mutations unique to cancer cells, but very few mutations were unique to the metastatic brain tumor. Instead, the major difference between the two tumor types was the relative frequency of the individual mutations in each tissue sample. Twenty of the 48 mutations occurred occasionally in cells in the primary tumor but were quite common in the metastatic tumor, suggesting that a small cohort of cells present in the primary tumor drove the cancer’s spread. “It’s as if a small subset of cells broke off from the primary tumor, circulated through blood, found a new home in the brain, and began to grow wildly and out of control,” says Richard Wilson, director of the Genome Sequencing Center at Washington University and a senior author of the paper.