From BRCA to HRD testing in ovarian cancer


BRCA mutations represented the first biomarker for precision oncology in ovarian cancer. Samples with ovarian cancer and BRCA mutations were found to be highly sensitive to a specific class of targeted agents, the inhibitors of the PARP enzyme (PARPi). 

The presence of mutations in the BRCA1 or BRCA2 genes leads to a deficiency of the DNA damage repair pathway based on homologous recombination (homologous recombination deficiency, HRD). However, a similar deficit can be caused by epigenetic or genetic alterations in various genes involved in the HR pathway. In fact, HRD has been found in about 50% of ovarian cancer cases, while somatic or germline BRCA mutations are detected in about 20% of cases. 

Clinical studies have shown that PARPi are also effective in non-BRCA mutant HRD positive samples and, therefore, it is essential to identify this biomarker in clinical practice. The methods for the detection of HRD used in clinical practice and clinical research are based on the identification of pathognomonic genomic alterations of HRD. Indeed, this condition is associated with widespread genomic damage which is often described as a genomic scar that can be identified with targeted sequencing approaches. 

Following a technology overview by Dr. Elaine Wong-Ho, Dr. Normanno will present the experience of his laboratory evaluating the Ion Torrent Oncomine Comprehensive Assay Plus*, a targeted NGS approach that can help clinical research in identifying all relevant biomarkers now including also HRD.

Webinar Learning Objectives:

  • How and why HRD is being measured currently by leading labs
  • Understand the importance of BRCA to HRD testing in ovarian cancer
  • How the Genomic Instability Metric compares to other orthogonal methods.

*For Research Use Only.

Dr. Nicola Normanno

Director, Translational Research, National Cancer Institute, Italy - Pascale Foundation

Dr. Normanno, MD earned his Medical Doctor Degree in 1988 at the Medical School, University of Naples (Italy) Federico II. After a residency in Oncology at the Oncology Department of the same university, in 1991 he achieved the specialisation in Medical Oncology, and in 2001 in Haematology.
Between 1990 and 1993, Dr Normanno did a postdoctoral fellowship at the Tumor Growth Factor Section, Laboratory of Tumour Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. After being senior Investigator and later Acting Chief (2004-2005) at the Experimental Therapy Section, INT-Fondazione Pascale, Naples, Dr Normanno is currently Chief of the Cell Biology and Biotherapy-Unit at the same Hospital, and since 2006 also Director of the Translational Research Department.
Since 1993 Dr Normanno’s area of research has been the study of the role of growth factors and receptors of the EGF family in the pathogenesis of solid tumours; the use of antisense oligonucleotides and inhibitors of receptors in experimental models of molecular therapy of carcinomas; identification of markers of response or resistance to anti-EGFR agents.
Dr Normanno is a member of the European Society for Medical Oncology (ESMO), the American Association for Cancer Research (AACR), the Italian Association of Medical Oncology (AIOM), and the Italian Cancer Society (SIC). He is from 2018 President of the International Quality Network for Pathology (IQN Path) and President Elect of the Italian Cancer Society (SIC). Dr Normanno is a reviewer for several peer reviewed journals among which: Annals of Oncology, Breast Cancer Research and Treatment, Clinical Cancer Research, International Journal of Cancer, European Journal of Cancer, British Journal of Cancer, Nature Communications. He is also Associate Editor of BMC Cancer and Gene. Dr Normanno is the author of over 200 papers published in peer reviewed journals.

Dr. Elaine Wong-Ho

Oncology Product Manager, Clinical Sequencing Division, Thermo Fisher Scientific

Dr Wong-Ho earned her PhD in Molecular and Medical Pharmacology at the University of California, Los Angeles, studying the viral pathogenesis, from oncolytic herpesviruses to human coronaviruses.
Her professional career includes 15 years in the life sciences industry, spanning tools and assay development from microfluidics, automation to single cell sequencing. As an Oncology product manager at Thermo Fisher Scientific, she is responsible for the developing and managing comprehensive genomic profiling assays.
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