Newsroom

October 15, 2019

New Data from Ambry Genetics Demonstrates Impact of First Major Advancement in Over 10 Years to Increase Diagnostic Yield in Genetic Testing for Hereditary Cancer Risk

In a prospective study, the addition of RNA genetic testing to hereditary cancer panels identified more disease-causing mutations in patients compared to DNA-only testing and clarified inconclusive results.

Separate data showed RNA genetic testing’s ability to clarify the interpretation of complex mutations associated with hereditary cancer risk

(Aliso Viejo, CA) October 15, 2019: Ambry Genetics (Ambry), a leading clinical genetic testing lab, will present data at the American Society of Human Genetics (ASHG) annual conference this week from the first prospective study of paired RNA and DNA genetic testing for hereditary cancer risk, called +RNAinsight™. The data from this study of the first 1,000 patients to receive +RNAinsight show a significant increase in diagnostic yield (identifying mutations in our DNA as disease-causing) compared to DNA testing alone. This is the first major increase in diagnostic yield for hereditary cancer risk in over 10 years. Through +RNAinsight, Ambry is the first and only lab to offer paired RNA and DNA genetic testing for hereditary cancer as a commercially available clinical test.

Standard DNA testing excludes large portions of DNA, thereby missing some mutations that cause increased risks for cancer. In addition, DNA testing for hereditary cancer risk can produce inconclusive results and fail to determine that a variant (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 steps, or certain therapeutic treatments, and relatives may not be referred for genetic testing and subsequently may not be referred for necessary high-risk surveillance. Adding RNA to DNA testing overcomes these limitations for a substantial number of patients as RNA provides considerably more evidence than DNA alone about whether our DNA has variants that increase cancer risk.

At ASHG, Ambry will present data showing that +RNAinsight both (1) identified new variants that increased cancer risk and that would have been missed with DNA testing alone, and (2) determined whether certain variants actually increased cancer risk even though DNA testing alone would have been inconclusive and left doctors without this crucial information.

“Combining RNA and DNA genetic testing lets more people know they have genetic mutations that increase their risks for cancer, empowering them to take action to better manage their cancer risks,” said Tyler Landrith, Ph.D., an Ambry scientist who will present the study. “+RNAinsight is the first major, genetic-testing advancement in over 10 years to increase diagnostic yield for hereditary cancer risk.”

Dr. Landrith will present data from a prospective analysis of 1,000 patients who received RNA genetic testing (for up to 18 genes). The data show a relative increase in diagnostic yield of 9.1 percent more than DNA testing alone. Adding RNA genetic testing also resulted in a 5.1 percent relative decrease in the number of patients that would have received inconclusive results with DNA testing alone and would not have learned whether they had increased cancer risk.

The prospective study also validated the accuracy of +RNAinsight, establishing a large control dataset of healthy patients. This dataset allowed Ambry researchers to establish a baseline for benign and disease-causing mutations across the genes tested. Dr. Landrith will address the validation in his presentation. In addition to the prospective study,  Ambry Senior Research Associate Blair Conner, M.S., will present data at ASHG showing that RNA genetic testing provided additional evidence to clarify the interpretation of 15 complex variants in genes associated with increased risks for breast, ovarian, colorectal, uterine, and other cancers. Without RNA genetic testing, these variants
would have remained inconclusive. This means that past, current, and future patients who otherwise would not have learned they have increased risks for these cancers will now have crucial information to more precisely tailor their medical management for the prevention, early detection, and treatment of cancer.

“An inconclusive result can be unsettling for patients, especially for patients with a strong family history of cancer. Both clinicians and patients may worry that current technology has missed disease-causing mutations in the genes tested,” said Ms. Conner. “These data show how +RNAinsight was able to overcome the technological limitations of DNA genetic testing by turning inconclusive results into actionable information for clinicians to better guide patient care.”

+RNAinsight is now available through doctors and genetic counselors around the country. For more information on RNA genetic testing, please go to www.ambrygen.com/RNAinsight.

For the full list of studies that will be presented at ASHG, please see below:

Oral Presentations:
Wednesday, October 16, 1:00PM - 2:00PM
Session 112, Room 310A, Level 3, Convention Center

Exome and RNA-based Sequencing Methods for Variant Interpretation to Improve Clinical Utility
1:15PM | #197 High-throughput RNA splicing profile increases detection of clinically-actionable variants while reducing inconclusive results in patients with hereditary cancer predisposition. T. Landrith, B. Li, A. Cass, B.R. Conner, S. Wu, H. Vuong, S. Charpentier, J. Burdette, H. LaDuca, T. Pesaran, J. Rae-Radecki Crandall, H. Lu, B. Tippin-Davis, A. Elliott, R.Karam.
1:45PM | #225 Reclassification of splicing VUS in neurological disease genes via RNA-seq. S.Ichikawa, B.R. Conner, S. Wu, R. Karam.

Poster Presentations:
Poster# 990W: Wednesday October 16, 2:00PM - 4:00PM
Leveraging tumor characteristics to predict germline variant pathogenicity in mismatch repair genes. S. Li, D. Qian, B.A., Thompson, S. Gutierrez, T. Pesaran, H. LaDuca, H. Lu, E.C. Chao, M.H. Black.
Poster# 2449T: Thursday October 17, 2:00PM - 4:00PM
RNA-seq identifies structural variants in hereditary cancer genes. B. Conner, M. Richardson, F.Hernandez, T. Landrith, T., McBride, B. Tippin-Davis, R. Karam.
Poster#1454F: Friday October 18, 1:00PM - 3:00PM
Accounting for splicing effects in known missense variants improves in silico prediction of deleterious effect. D. Qian, J., Clifford, A. Tchourbanov, Y. Tian, M.H. Black, H.M. Lu, Z. Zhu, S. Li.

For more information on risk factors for hereditary cancer, please visit cancer.gov’s fact sheet on hereditary cancer and genetic testing.