8PDIAGNOSTIC NEXT-GENERATION SEQUENCING PANEL FOR HEREDITARY BREAST AND OVARIAN CANCER

Familial clustering of breast and ovarian cancer is seen in ∼15% of cases. BRCA1 and BRCA2 are the major genes responsible for hereditary breast and ovarian cancer. Nonetheless, BRCA1 and BRCA2 mutations are found only in ∼25% of suspected cases. Other genes conferring an increased risk for breast and ovarian cancer are known, but patients are not routinely tested for mutations in these additional genes due to high expense both in time and costs. The development of next-generation high-throughput sequencing gives the opportunity to test dozens of candidate genes simultaneously at high speed and low costs. We have developed a diagnostic panel comprising 30 known susceptibility genes for breast and ovarian cancer to find causative mutations. Here we present the methodology of the diagnostic panel (Target enrichment, NGS library preparation and sequencing, bioinformatic analysis and medical evaluation) as well as cases of mutations in non-BRCA genes discovered with our diagnostic cancer panel. Samples are sequenced with a high coverage per base and can be multiplexed. Combined with bioinformatic analyses, rare variants and mutations can easily be detected. The diagnostic panel offers the chance to detect causative mutations in families highly suggestive of an increased familial risk, especially after negative testing for BRCA1 and BRCA2. The chance to find a non-BRCA causative mutation in such a family is estimated to be at least 25%. Knowing the disease-causing mutation in a familiy enables genetic testing for at-risk relatives and preventive measures. Disclosure: M.M. Menzel, T. Scheurenbrand, A. Sprecher, M. Schubach, F. Battke: Employee of CeGaT GmbH; S. Biskup: CEO of CeGaT GmbH