Ambry Genetics

Pairing RNA with DNA Genetic Testing Improves Risk Assessment for Hereditary Cancers Interview with:
Ambry Genetics Rachid Karam, MD PhD

Director, Ambry Translational Genomics Lab
Ambry Genetics What is the background for this study?

Response: Standard DNA testing for hereditary cancer risk excludes large portions of DNA, thereby missing some mutations. In addition, DNA testing can produce inconclusive results and fail to determine that an error in our DNA increases cancer risk. These limitations impact patients and their families because doctors may not have the information needed to recommend appropriate preventive, early detection, or therapeutic steps. Additionally, relatives may not be referred for genetic testing and obtain the care they would otherwise have gotten if they had learned they had mutations. The study looked at how the addition of RNA genetic testing to standard DNA testing for hereditary cancer risk was able to increase diagnostic yield.

The study looked at the first 2,500 patients that received Ambry Genetics +RNAinsight™, paired RNA and DNA genetic testing for hereditary cancer risk. The data from this study showed that the addition of RNA genetic testing to DNA testing (1) identified new mutations that would have been missed with DNA testing alone, and (2) clarified inconclusive results as disease-causing. What are the main findings?

  • Response: As a result of +RNAinsight, the data show an overall relative increase in diagnostic yield of 6.7 percent compared to DNA testing alone, increasing by as much as 19 percent for specific genes (ATM:19%, PMS2:17%, BRCA1:14%, MSH2:13%, MUTYH:11%, CHEK2:7%, BRCA2:5%).
  • The addition of RNA genetic testing resulted in an overall 4.5 percent relative decrease in the number of patients that would have received inconclusive results with DNA testing alone, reducing inconclusive results by as much as 9 percent in specific genes (MUTYH:9%, MSH2:8%, BRCA2:7%, CHEK2:7%, PTEN:4%, ATM:4%, PMS2:3%, APC:2%). What should readers take away from your report?

Response: Hereditary cancer panels should include both RNA and DNA genetic testing. By looking at regions of the gene that other tests don’t, +RNAinsight reduces false negatives, maximizing the number of patients who learn they have higher risks for hereditary cancer.

Previous studies from Ambry Genetics have looked at how retrospective RNA genetic testing improved diagnostic yield and these retrospective studies found substantial loss to follow-up.

The data also highlight the huge difference between medical–grade genetic testing and direct-to-consumer genetic testing, which is already limited in the variants their tests can detect and report, and now, with +RNAinsight, fall even further behind. What recommendations do you have for future research as a result of this work?

Response: We will continue to expend the number of individuals tested. The more people we test, the better we will be able to fully understand the impact RNA testing has in specific diseases, such as hereditary breast and ovarian cancer. 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.


Abstract Unparalleled Clarity and Mutations:
Clinical RNA Testing Provides Answers Beyond DNA

Presented at National Society of Genetic Counselors Annual Conference
Salt Lake City, Utah


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Last Modified: Nov 26, 2019 @ 10:03 pm

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