RNA Genetic Testing Improves Analysis of Hereditary Cancer Genes

MedicalResearch.com Interview with:
Rachid Karam, PhD

Director, Ambry Translational Genomics Lab
Ambry Genetics 

MedicalResearch.com: What is the background for this study?

Response: DNA genetic testing (DGT) for hereditary cancer genes is now a well accepted clinical practice; however, the interpretation of DNA variation remains a challenge to laboratories and medical providers.

RNA genetic testing (RGT) as a supplement to DGT is a means to clarify the clinical actionability of variants in hereditary cancer genes, improving our ability to accurately apply known strategies for cancer risk reduction.

MedicalResearch.com: What are the main findings?

Response: In this study, RGT clarified the genetic test in almost 90% of cases evaluated. For all tested variants of hereditary cancer, RGT reclassified 86% of the results.  This was primarily due to reclassification of variants of uncertain significance as either clinical actionable (Pathogenic/Likely Pathogenic) or benign based on the RNA evidence. Results from a follow-up survey sent to all medical providers who received a reclassification report for these variants showed that RGT results translated directly into clinical management updates for these patients particularly for those who changed from Variant of Uncertain Significance to Very Likely Pathogenic. 

MedicalResearch.com: What should readers take away from your report?

Response: RGT as a supplement to DNA genetic testing improves the classification of variants identified in hereditary cancer predisposition genes, and is expected to affect medical management in at least 1 in 50 patients.

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response:  Perform a prospective study, to evaluate the impact of RGT on patients who have not been selected by previous DNA results.

MedicalResearch.com: Is there anything else you would like to add?

Response: Based on the variant classification improvements and impact to patient care, Ambry is gearing up to offer RNA genetic testing in the healthcare setting. We have completed the clinical validation, and look forward to making this available to healthcare providers and their patients this year.


This study was conducted by Ambry Genetics, where I am employed. 



RNA Genetic Testing in Hereditary Cancer Improves Variant Classification and Patient Management

Top Rated Poster

  • RNA genetic testing (RGT) as a supplement to DNA genetic testing (DGT) improves variant classification in hereditary cancer predisposition testing.
  • RGT is expected to affect medical management in at least 1 in 50 patients who undergo DGT.
  • Specifically, in the case of splicing variants identified in clinically actionable genes, the reclassification of these germline alterations as either disease-causing or neutral proved to be a fundamental step to alter medical management.
  • Authors: Rachid Karam; Kate Krempely; Marcy Richardson; Kelly McGoldrick; Blair R. Conner; Tyler Landrith; Kyle Allen; Amal Yussuf; Huma Rana; Samantha Culver; John Lee; Sarah Nashed; Deborah Toppmeyer; Debra Collins; Ginger Haynes; Tina Pesaran; Holly LaDuca; Jill Dolinsky; Elizabeth Chao
  • Collaborators: Cedar Sinai Medical Center; Dana Farber Cancer Institute; Rutgers Cancer Institute of New Jersey
  • Conference: Annual Clinical Genetics Meeting (ACMG) 2019
  • Date: Thursday, Apr 04, 2019 

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Apr 18, 2019 @ 12:24 pm




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