Ambry Genetics

Additive Benefit of RNA Genetic Testing for Hereditary Cancer Interview with:
Ambry GeneticsRachid Karam, MD, PhD
Ambry Genetics
Aliso Viejo, California What is the background for this study?

Response: DNA genetic testing is a powerful tool used to tailor medical care based on an individual’s cancer risk. However, even medical grade DNA genetic testing can produce inconclusive results, finding a change in our DNA to be a variant of unknown significance (a VUS) and failing to determine whether it increases cancer risk. When this happens, healthcare providers might not have the information needed to recommend appropriate preventive and early detection steps, or certain cancer treatments, and relatives may not be referred for genetic testing for their own care.

In this study, investigators from Ambry, Dana-Farber Cancer Institute, Cedars-Sinai Medical Center, Rutgers Cancer Institute, and University of Kansas Cancer Center demonstrated that performing both DNA and RNA genetic testing reduces inconclusive results enabling clinicians to offer cancer screening and treatment resources to the right patients. What are the main findings?

Study main findings:

  • RNA genetic testing provided additional evidence to clarify the interpretation of DNA genetic testing results and could provide more accurate test results for one out of every 43 patients undergoing genetic testing for hereditary cancer risk. 
  • When assessing the types of variants identified in 307,812 patients who had undergone standard DNA testing at Ambry Genetics for hereditary cancer, the study determined that 7,265 – or one in 43 patients – could benefit from paired RNA and DNA genetic testing. Given that 700,000 people in the United States are expected to receive genetic testing for hereditary cancer risk in 2019, more than 16,000 individual results could change and be clarified with RNA genetic testing annually.
  • RNA genetic testing clarified 88 percent of 56 select variants of unknown significance, determining that 47 percent were disease-causing, and 41 percent were benign.
  • The study also found that determining whether a variant of unknown significance is actually disease-causing can substantially impact patient care. 44 percent of the clinicians whose patients received clarified results (and who responded to a study survey) changed their care for those patients, and 78 percent of them changed their care for patient relatives. What should readers take away from your report?

Response: Genetics is a field that is always evolving, and this study demonstrates that medical grade genetic testing laboratories need to invest in innovation to be able to translate scientific breakthroughs into the clinical practice. The study shows that with the addition of RNA genetic testing over 16,000 more patients each year will learn if they have genetic variations that increase their risks for cancer and take action.

This article also highlights the huge difference between medical grade genetic testing and direct-to-consumer (DTC) genetic testing, which is already limited in the variants their tests can detect and report, and now falls even further behind. What recommendations do you have for future research as a result of this work?

Response: The study showed that only 10 percent of patients invited to receive RNA genetic testing after having undergone DNA testing sent in samples. Given the substantial loss-to-follow-up from retrospective RNA testing and the proportion of patients estimated to benefit, in the future it will be important to evaluate the impact of performing RNA genetic testing for patients at the same time as DNA testing. Is there anything else you would like to add?

Response: Ambry has made RNA genetic testing available to all patients at the same time as DNA testing through +RNAinsight, which is now available through doctors and genetic counselors around the country. For more information, please go to

With regards to disclosures, I am an employee of Ambry Genetics.


Karam R, Conner B, LaDuca H, et al. Assessment of Diagnostic Outcomes of RNA Genetic Testing for Hereditary Cancer. JAMA Netw Open. Published online October 23, 20192(10):e1913900. doi:10.1001/jamanetworkopen.2019.13900


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Oct 23, 2019 @ 9:51 pm

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