Understanding the genetic changes that lead to different cancers is key to more effective diagnosis and treatment of the disease. And thanks to the availability of faster, cheaper genome sequencing technologies, researchers are now able to peer more deeply into the DNA of cancer cells than ever before.
Recent studies have sequenced more than 600 genes in both brain and lung cancer samples and found novel patterns of gene mutation. But in both of these studies, the findings were limited to genes the researchers already suspected of involvement in cancer.
Now researchers from Washington University in St. Louis have taken an unbiased approach to finding mutated cancer genes and found that half of the ones they identified were completely unexpected. The researchers describe their work in a paper published online today by Nature.
“In the past, cancer researchers have been ‘looking under the lamppost’ to find the causes of malignancy – but now the team from Washington University has lit up the whole street,” said Francis Collins, former director of the National Human Genome Research Institute, in a statement.
Instead of looking at a subset of genes already thought to be involved in cancer, the Washington University researchers cast their net as broadly as possible by sequencing the complete genomes of an acute myeloid leukemia (AML) patient’s normal and tumor cells.
Nearly 2.7 million variations in the DNA of the patient’s tumor were initially flagged, but almost 98% of these were also found in the patient’s normal cells, indicating that these mutations were in her genome from the beginning and not the root of her cancer.
The researchers then used a variety of methods to further narrow down the field of mutations that might be responsible for the patient’s cancer. They were ultimately left with single-base mutations in just eight genes. Half of those eight were in gene families already strongly associated with cancer in general, while the other four occurred in genes not previously implicated in the disease. None of the eight mutations had previously been reported for AML before. Nor could any of them be found in the tumors of an additional 187 AML patients the researchers tested.
“This suggests that there is a tremendous amount of genetic diversity in cancer, even in this one disease,” team leader Richard Wilson said in statement. “There are probably many, many ways to mutate a small number of genes to get the same result, and we’re only looking at the tip of the iceberg in terms of identifying the combinations of genetic mutation that can lead to AML.”
Although the results of this study can’t tell a doctor how to treat better treat a patient, the research is an essential first step down the path towards developing targeted therapies, said Brian Druker, a cancer genetics researcher whose own work helped with the development of the targeted cancer drug Gleevec, in a statement.
“This tour-de-force effort identified a small number of mutations in genes that no one predicted, and their uniqueness for this patient begins to give us a glimmer of the genetic complexity and diversity of this disease,” he said.