Improving hereditary cancer diagnostics using RNA sequencing: Lessons from a 43K patient study with Rachid Karam, M.D., Ph.D.

  • Genes involved in many of the known inherited cancer susceptibility syndromes (more than 50 hereditary cancer syndromes described in the scientific literature) have been identified. As such, patients with a family history of certain cancers can perform genetic testing to confirm whether a condition is indeed the result of an inherited syndrome. Additionally, family members who have not (yet) developed a cancer can check if they inherited the same variant as a family member who is known to carry a harmful (cancer susceptibility predisposing) variant. Examples of such genetic tests include BRCA1 and BRCA2 genes associated with hereditary breast and ovarian cancer syndrome (HBOC) and the APC and DNA mismatch repair genes associated with colon cancer.

    There are technical and logistical limitations that hinder the identification of individuals at risk for hereditary cancer, resulting in many patients who undergo DNA genetic testing going undiagnosed. In this webinar we will review splicing data obtained from a cohort of over 43,000 individuals tested for cancer predisposition and demonstrate how RNA sequencing improves the diagnostic yield of genetic testing. A splicing profile performed in this clinical cohort demonstrated that over 6% of DNA variants identified result in abnormal splicing. It also led to the detection of novel deep-intronic mutations in patients who otherwise would have a negative or inconclusive result, representing approximately 1% of all pathogenic mutations identified in this study.

    Rachid Karam, director of translational and clinical research at Ambry Genetics in Aliso Viejo, California, will:

    • Explain current technological limitations to identifying patients with or at risk for hereditary cancer
    • Demonstrate how RNA sequencing can improve the positive yield of DNA genetic testing for hereditary cancer
    • Highlight results from a cohort of 43,000 individuals tested for cancer predisposition by paired DNA and RNA sequencing
    • Provide examples of cryptic “deep-intronic” alterations identified in the cohort
    • Answer your questions live during the broadcast.

    This webinar will last for approximately 60 minutes.


Director, RD - Translational & Clinical Research

Dr. Karam obtained his M.D. in 2003 in Brazil, and his Ph.D. in oncogenetics in 2008, at the University of Porto, Portugal. He did his postdoctoral studies at the University of California, San Diego, from 2009 to 2014. He joined Ambry Genetics in 2014 and is now Ambry’s director of translational and clinical research. He also actively participates in several U.S. National Institutes of Health (NIH)/ClinGen committees dedicated to creating guidelines for the interpretation of genetic testing and is currently the cochair of ClinGen’s CDH1 Variant Curation Expert Panel.

Jackie Oberst, Ph.D.

Washington, DC

Dr. Oberst did her undergraduate training at the University of Maryland, College Park, and her Ph.D. in Tumor Biology at Georgetown University, Washington D.C. She combined her interests in science and writing by pursuing an M.A. in Journalism from the Philip Merrill College of Journalism at the University of Maryland, College Park. Dr. Oberst joined Science/AAAS in 2016 as the Assistant Editor for Custom Publishing. Before then she worked at Nature magazine, the Howard Hughes Medical Institute, The Endocrine Society, and the National Institutes of Mental Health.

  • Wed, October 13, 2021
  • 9:00am PDT
  • Duration: 1 hour
  • C.E.U. --
  • P.A.C.E. --

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