Very Personalized Medicine: Sequencing of Second Cancer Patient Reveals Potentially Significant Mutations

DNA Strand

A new genetic screening process has helped researchers understand the genetic causes of cancer, such as how mutations accumulated in a person’s life can cause leukemia.

The study shows that by comparing a person’s own DNA to that of their cancerous cells, researchers can find DNA mutations that may have led to abnormal cell growth, or cancer.

After sequencing a single leukemia patient’s healthy and cancerous DNA, researchers at Washington University School of Medicine in St. Louis were able to pinpoint several mutations out of hundreds that appeared likely to have contributed to his cancer’s development. He is the second patient with acute myeloid leukemia (AML) to have his entire genome and that of his cancerous tissue fully sequenced, rather than just the portions that are known to be prone to cancer-causing mutations.

“If we only look at genes with known or suspected links to cancer, we’ll miss many mutations that are potentially relevant,” co-author Richard Wilson said in statement.

The study by Mardis et al., published in The New England Journal of Medicine, identified a total of 750 mutations in the patient’s AML genome. Most of them proved irrelevant, but 64 were likely to be cancer-related. Two previously known mutations were newly linked to leukemia.

Timothy Lay, senior author of the study, explained in a statement that most patients with this type of leukemia are treated similarly, at least in the beginning. This study’s patient, for example, received various chemotherapy drugs. Defining cancer mutations could help determine which patients need aggressive treatment, such as a stem cell transplant, and which could be effectively treated with less intense therapies.

Personalized sequencing of entire cancer genomes is possible now because the accuracy and cost of genome sequencing technology has dramatically improved. This study took only a few months at one-third the cost of the first AML patient, who was sequenced only one year ago.

To date 350 cancer mutations are known, but thousands of cancer genomes will need to be screened to truly explain the genetic basis for cancer. This information could be used not just to guide physicians to the most effective treatment, but also to inform patients about their prognosis.

But do patients even want to know?

A recent study published in the Journal of Genetic Counseling suggests they do. Researchers found that 98 of 99 patients with ocular melanoma, a rare, untreatable eye cancer, said they wanted to know if their cancer had a genetic marker that gave them a 50 percent chance of dying within five years. Patients were relieved when the risk was low, but even when the risk was high they were enabled to plan financially and make the most of their time alive.

This very personalized medicine will continue to be driven by improved diagnostic testing, finding more predictive disease markers, and new therapies directed at cancer-specific mutations, James Downing wrote in a recent editorial published this month in The New England Journal of Medicine. He believes this technology will likely be used clinically long before we have a complete knowledge of cancer genes.


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