I have often remarked that different genetic testing laboratories may give different results and suggested that people not automatically accept the results of one laboratory when planning their futures. This is especially true when major life decisions are involved.
A recent report from the IOS Press, published online by newswise introduces the situation for a specific genetic test as follows:
For individuals who develop colorectal cancers at a young age or have a family history of such cancers, microsatellite instability testing (MSI) has become an almost standard component of clinical evaluation. This DNA-based test can uncover hereditary nonpolyposis colon cancer syndrome (HNPCC), also called Lynch’s syndrome. However, despite the increased use of this test, there have been no reports of how well the results from any given laboratory agree with any other laboratory. In an article in the current issue of Cancer Biomarkers, researchers conducted testing across 6 laboratories to evaluate variability in reported results.
Here's what was done:
The six laboratories, located in the United States, Canada, and Australia, were members of the Cooperative Family Registry for Colon Cancer Studies (also called the Colon CFR). Using tumor samples collected since 1998 through the CFR, MSI testing was done at the six laboratories. Three of the laboratories had more than 8 years each of prior experience in MSI testing, while the other three set up MSI assays specifically for the Colon CFR.
The results--and follow-up--were very interesting:
When the result showed wide disagreement with no systematic trends, one of the most experienced laboratories was designated the “gold standard†reference facility. With further testing of samples among the most experienced laboratories, the credentials of the reference laboratory were validated. A review of the results from all of the facilities resulted in five key rules that laboratories should observe when conducting MSI testing. Using these lessons learned, a final set of testing showed much improved agreement across all six laboratories.
The complete article, “Ascending the Learning Curve – MSI Testing Experience of a Six-Laboratory Consortium†by Noralane M. Lindor et al appears in a special issue of Cancer Biomarkers and is available by subscription only. I'll try to get a reprint and post it to the geneforum resources. Unfortunately, I cannot even tell you which laboratory was found to be the "gold standard", but I will try to find out.
The tendency to believe the results of a single genetic test may result in part from our acceptance of technology we don't fully understand. We may also each have an inborn or learned tendency to accept a diagnosis, figuring that tests are generally accurate. How far we challenge a result, or how often we look for a second opinion, may be dictated by our personal feelings, our insurance coverage, and or general outlook on life.
I think what matters in this particular article, and the study on which it is based, is that testing can itself be tested. The lead author, Noralane M. Lindor states,
This experience flushed out some important principles in MSI testing…and demonstrated that a very high degree of concordance for MSI testing is feasible….We strongly urge all clinical and research laboratories conducting MSI to participate in a sample exchange validation with an experienced group or consortium and that clinical laboratory certifying bodies develop plans to evaluate quality of MSI testing results being returned to clinicians and patients.
We as consumers can encourage studies of this type and help make testing more reliable--even if we don't know all the intricate details involved in the testing and its interpretation.
Marie Godfrey, PhD
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