Tuesday, 16 October 2018

The Results of Your Genetic Test Are

Genetic Test Are Reassuring.

The Results of Your Genetic Test Are Reassuring. But That Can Change.

The results of a genetic test could seem final — in any case, a point mutation is present or it's not.

That mutation increases the danger of a disease, or it doesn't.

In fact, those findings aren't as straightforward as they could seem, and therefore the consequences may have grave implications for patients.

While a person’s genome doesn’t change, the research linking particular bits of DNA to the disease are very much in flux.

Geneticists and testing labs constantly receive new information that leads them to reassess genetic mutations.

As a result, a mutation seen as benign today could also be found dangerous tomorrow. And vice versa. But there's no great way to urge the new information to doctors and patients.

The result: The gene test you had a couple of years ago might yield a startlingly different result now.

The problem affects a minority of patients, mostly people with unusual mutations.

The more common disease-causing mutations — like people who predispose you to breast or colon cancer — are so well studied that their meaning isn't unsure.

In a recent study, researchers at Myriad Genetics, the diagnostic company, reviewed data on 1.45 million patients who had genetic tests from 2006 to 2016 to ascertain if the results originally reported still held true.

The lab issued new reports for nearly 60,000 of them, meaning the old results had been superseded by new data.

But many patients who carry mutations that are reclassified remain within the dark.

“The system is completely chaotic,” said Dr. Sharon E. Plon, a clinical geneticist at Baylor College
of Medicine.

There is no systematic way, she said, to inform patients and doctors that a mutation once thought harmless has been shown to be a hazard or one thought dangerous is actually benign.

“Some labs return only one-time results,” said Dr. Theodora Ross, director of the cancer genetics program at the University of Texas Southwestern center.

“They are not going back to reassess test interpretations from ten years ago unless doctors ask.” But doctors seldom ask, she added.

Normally, a doctor orders genetic testing for an individual with a robust case history of, say, heart attacks, strokes, or cancer. A sample of a patient’s blood or saliva is shipped to a lab, where the patient’s DNA is scanned for unusual alterations.

Not all of these are harmful. The lab compares the mutations to those shown in scientific studies to cause disease.

Some patients are told they need a mutation that's meaningless. Others learn they have “a variation of unknown significance” during a suspect gene — meaning nobody knows quite what to make of it.

Still, other patients have a mutation deemed dangerous, meaning there's a really high risk of developing cancer, heart disease, or other condition.

For those patients, such a result can mean regular monitoring and may alter a variety of life decisions, including whether to possess children.

Reclassification may be a particular problem for members of racial and ethnic minorities  populations whose genes haven't been also studied as those of the White race.

It can be difficult to understand what a variation in DNA means for these patients.

A federally-supported database, ClinVar, allows laboratories to publicly share data on genetic mutations and what they're thought to mean. But some companies, like Myriad, which host huge databases on genetic mutations, don't contribute to ClinVar.

Even the terminology for DNA variants might not be widely shared. Different labs have different naming schemes.

For example, ClinVar renders one DNA variant this way: ( NM_004004.5(GJB2):c.101T>C (p.Met34Thr).

But another lab does it like this: ( c.101T>C, p.Met34Thr, GJB2. )

Patients checking out information on their own “would not make certain what to type into ClinVar,” said Dr. Heidi Rehm, a clinical geneticist at Massachusetts General Hospital and therefore the Broad Institute.

In addition to the terminology problem, Dr. Ross said, there is a problem of discordance among labs.

When one big lab “reports a reclassification and therefore the other labs don't, and you've got family members who get tested at different labs, we've different interpretations of an equivalent patient data,” Dr. Ross said.

“How do we deal with that? What do we tell our patients?” Labs like Myriad often notify a doctor who ordered a genetic test when the results were reclassified. But even once they do, doctors might not be ready to reach and inform their patients.

“I’ve changed my practice location over the years, and my patients have moved,” Dr. Plon said.

“I have received updated reports for patients who not sleep in Houston, and we have no idea where they live.”

Some geneticists say the burden for getting updated results will fall on patients whose genetic alterations are rare ones. They will need to contact their doctors or genetic counselors annually to ask if there was a reclassification.

Reclassification is not always good news.

Dr. Jason Park, clinical director of the advanced diagnostics laboratory at Children’s Medical Center in Dallas said he has told parents of youngsters with severe epilepsy that a genetic mutation thought to be the explanation for the disease actually maybe a benign change.

The reclassification might not alter treatment since there often is not any specific treatment for a mutation thought to be causing severe epilepsy. But now parents who thought they had found the explanation for their child’s illness learn instead of that, the cause is unknown.

“For families, this will be a serious social issue,” Dr. Park said.

“There are support groups centered around certain genes. Now they're not a part of that group.”

But for some, like Ricky Garrison, a 61-year-old firefighter who lives in Denton, Tex., reclassification can be a lifesaver.

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