Cancer researchers urge double-checking gene tests used in treatment decisions
Stephanie Gomez, a research assistant works with urine and blood samples that will be used in gene mapping, in Falls Church, Va., on Monday, Sept. 30, 2013. (AP Photo/Carolyn Kaster)
WASHINGTON -- More cancer patients are getting the genes in their tumors mapped to help guide their treatment. New research suggests that isn't always accurate enough, and a second test could help ferret out the culprit genes.
Cancer involves two sets of genetic code -- your own and your tumour's. Wednesday's study found that mapping only the tumour's genome could provide misleading results and lead to treatment that's less likely to work.
Comparing the two genomic sequences ensures that a mutation found in a tumour really helped fuel that cancer and isn't a harmless mutation sitting in the person's normal cells, too, explained lead researcher Dr. Victor Velculescu of Johns Hopkins University.
That's important as scientists increasingly design drugs to target specific tumour mutations.
"We cannot have precision medicine without precision genomics. We can't expect physicians to provide the right therapy to the right patients if we can't obtain accurate results in our diagnostic tests," Velculescu said.
Tumour genetic tests often are simple, looking just for a single gene mutations or "hot spots" that match one of the first targeted therapies to hit the market. That's not the worry here. Velculescu's concern is broader genomic sequencing, or mapping, of potentially hundreds of suspicious gene variations.
This next-step testing isn't common yet, but it is expected to increase rapidly in the next few years. Some clinics sequence both the tumour and the normal tissue, while others sequence only the tumour.
To see if tumour-testing alone is enough, Velculescu's team analyzed records from 815 patients with 15 different types of cancer who had had both types of sequencing.
Nearly two-thirds of mutations found in the tumour-only testing turned out to be false-positives -- present in patients' normal tissue, too, when both genetic maps were compared, the team reported in the journal Science Translational Medicine. Then the researchers tried a more targeted approach, looking just for certain cancer-linked genes, and still one-third of abnormalities were false-positives.
The two-part sequencing takes more effort -- remembering to get a patient sample of healthy tissue -- and costs more, Velculescu said.
The study points out a key consideration as this genetic testing is poised to increase, said Dr. Matthew Ellis, a breast cancer genomics expert at Baylor College of Medicine.
"If you want to work out how the cancer recoded its genome to become a cancer, you have to be able to compare the cancer genome with the genome you inherited from your mom and your dad," said Ellis, who was not involved with the new study.
But the wide variety of genetic abnormalities the Hopkins team uncovered also highlights the need for more research to match medications with these variants so that more people can benefit, Ellis said.
The National Cancer Institute is beginning a major study to do that, part of a government push for precision medicine.