Genome sequencing has also engendered a new approach to cancer research. Last year, Elaine Mardis and her team at Washington University School of Medicine in St. Louis sequenced the complete genomes of cancerous and normal tissue in a patient with acute myeloid leukemia, identifying 10 mutated genes that appear to play a role in this cancer. This year, her team has sequenced the genome of four different types of tissue from a breast-cancer patient–the normal genome, DNA from the primary tumor, DNA from a metastatic brain tumor (a secondary tumor formed from cancer cells originally from the breast tumor), and DNA from the patient’s cancerous tissue implanted into a mouse. (Because the cancerous tissue removed during surgery is often inadequate for genetic research, scientists sometimes grow tumor tissue from the patient’s cancer cells in mice.)
While the vast majority of the sequence will be identical in all four samples, identifying differences could pinpoint the genetic changes that lead to the initial formation of the tumor, as well as those that trigger metastasis. If scientists can find drugs that block the primary tumor from spreading, cancer could be converted into a manageable chronic disease.
Mardis’s team has already identified a number of variants that are unique to either the primary tumor or the metastatic tumor. They have also found some variants that appear in both but are more common in the metastatic tissue, suggesting that this type of mutation might enable cells to spread through the body. “We are now looking at breast-cancer-derived brain, lung, and liver tumors to see if there are commonalities in metastatic disease,” says Mardis. Her center aims to sequence 150 cancer genomes this year. Next year, that number will likely seem small.