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1 Speakers SESSION 1 Clinical status and perspectives for hereditary breast and ovarian cancer (HBOC) risk prediction. Fergus Couch Mayo Clinic Cancer Center and the Center for Individualized Medicine, Diana Eccles University of Southampton, Southampton, UK Professor Eccles is the Head of the Cancer Sciences Academic Unit which incorporates the Southampton Cancer Research UK Centre, the Southampton Clinical Trials Unit and links closely through our clinical academics to Cancer Care at UHS. She continues to work as an NHS consultant in clinical cancer genetics which encompasses diagnosis and management of many different genetic conditions that predispose to tumour development in families. Rita Schmutzler University Hospital Cologne, Germany Fam. Breast and Ovarian Cancer Sabine Linn Cancer Institute, The Linn lab focuses on the development of prognostic and predictive markers for breast and ovarian cancer to guide systemic therapy decisions. SESSION 2 Identification of novel HBOC genes and variants Claus Storgaard Sørensen Biotech Research & Innovation Center, University of Copenhagen, Denmark My team is investigating genome maintenance pathways including their close links with cell proliferation control. We are particularly interested in familial breast and ovarian cancer where we focus on factors and mechanisms that limit tumorigenesis. Bjarni Jóhann Vilhjálmsson Center for Bioinformatics (BiRC), University of Aarhus, Denmark I am fascinated by genetics, and how small genetic differences leads to phenotypic diversity that shapes our lives. Fueled by curiosity, I have spent my research career on developing statistical methods for understanding the genetic architecture of traits and diseases. This includes methods for detecting genetic associations in genome-wide association studies, and more recently, polygenic trait prediction and genetic disease risk assessment. Stefano Annunziato Cancer Institute, Modeling of breast cancer using nongermline mouse model approaches.

2 SESSION 3 Analysis of the effects of HBOC gene variants on treatment response. Lisa Wiesmüller University Hospital Ulm, Germany Our laboratory has developed and/or established powerful assay systems for the quantitative and qualitative analysis of DSB repair, recombination and replication stress response mechanisms in immortalized and primary cells from different organs. Violeta Serra Vall d Hebron Institute of Oncology, Spain Identification of response biomarkers to targeted therapy using PDX models of breast cancer. Oded Kopper Hubrecht Institute, The main focus of my research is establishing new platforms for studying ovarian cancer. We are developing 3D culture systems that will support long-term expansion of ovarian cancer organoids, which would recapitulate both the diversity and heterogeneity of the disease. Fallopian tube (FT) and ovary surface epithelium (OSE) are believed to be the origin of high grade serous ovarian cancer (HGSOC), the most common type of ovarian cancer (~70%). Recently, we have established normal FT and OSE organoid systems. Using crispr-cas9 technology we genetically manipulate these organoids in order to investigate the role of different genes and pathways in the development of HGSOC. SESSION 4 Model systems and assays for the functional classification of HBOC gene variants. Bas Vroling Bio-Prodict, At Bio-Prodict we design and build information systems for protein (super)families, tailored towards fundamental and applied research in Protein Engineering and DNA Diagnostics. These systems contain large amounts of very heterogeneous but highly integegrated data, e.g. alignment-derived data, structure data and information extracted from the literature. I am currently exploring novel ways of applying machine learning technology to predict the effect of nssnps on protein function. Joey Riepsaame Sir William Dunn School of Pathology, University of Oxford, UK. Developing in vivo and in vitro crispr-cas9 approaches. Michel Cannieux Integrated DNA Technologies, The development of tools and solutions to facilitate Genome Editing. This includes development of effectors (Cas9 variants & Cas9 alternatives, and RNA triggers), controls, detection and visualization systems (fluorescence, PCR, NGS). Alvaro NA Monteiro Moffitt Cancer Center, We are interested in the role of germline and somatic genetic factors involved in cancer predisposition, initiation, progression, and response to therapy. Our focus has been on four cancer sites: lung, brain, breast, and ovary. The overarching theme across these cancer sites is the systems biology approaches and genetics to perform in-depth studies with a view to develop translational solutions to cancer therapy and prevention.

3 Peter Bouwman Cancer Institute, The focus of my research is on hereditary breast cancer, with special emphasis on the suppressor gene BRCA1. Together with my co-workers in the group of Jos Jonkers, I have generated several novel mouse models for BRCA1 associated tumorigenesis and used these to get more insight in the function of BRCA1 in tumor suppression and treatment response. Currently, I am focusing on the functional classification of BRCA1 sequence variants of unknown clinical significance. Maaike Vreeswijk Dept.of Human Genetics, University Medical Center, Our research is focused on the DNA damage response and the translation towards clinical applications. We have developed tools for the reliable assessment of the clinical significance of Variants of Uncertain Significance in breast and ovarian cancer susceptibility genes. Haico van Attikum Dept. of Human Genetics, Leiden University, We study how cells repair DNA damage in the context of chromatin and use our expertise to development assays for the functional analysis of sequence variants in cancer. Sean Tavtigian Huntsman Cancer Institute, University of Utah, SESSION 5 Novel insights in HBOC suppression and consequences for functional assays. Shyam Sharan Center for Advanced Preclinical Research, National Cancer Institute, Over the past decade, the overarching goal of our laboratory has been to understand the functional significance of human BRCA1 and BRCA2 variants of unknown clinical significance (VUS). We have used a mouse embryonic stem (ES) cells-based assay developed in our laboratory. Desired variants are generated in the human BRCA1 or BRCA2 gene in bacterial artificial chromosomes (BAC) using recombineering technology. These are then introduced into ES cells engineered to express a conditional-selectable allele of BRCA1 or BRCA2. The extent to which specific variants complement the lethality of ES cells with BRCA1 or BRCA2 deficiency and the known functions of these proteins in DNA repair cell and cycle regulation is used as a surrogate readout to decipher their association with risk of developing the disease.to assess the physiological significance of our findings, we are also engaged in generation of new mouse models. These models serve as power powerful tools that have improved our understanding of the effect of these variants on growth and development, hematopoiesis, fertility and tumorigenesis. Ralph Scully Beth Israel Deaconess Medical Center, Harvard University, Arnab Ray Chaudhuri National Cancer Institute, Using mouse models and a combination of single molecule, cell biological and biochemical approaches, we investigate the mechanisms underlying stability of the DNA replication process and its contribution to genome integrity. We are particularly focused on understanding how mutations in certain factors result in chemo-resistance in Breast and Ovarian cancers by mediating replication fork stability.

4 Organisers Marjanka Schmidt Our work focuses on the effects of genetic variants on risk of breast cancer subtypes, prognosis and long-term outcome of breast cancer. We investigate the interactions between germline variants and life style on the incidence of specific breast cancer subtypes, and the interactions between germline variants, tumor genetic and molecular characteristics, breast cancer treatment, and lifestyle factors on breast cancer prognosis, incidence of second tumors, and mortality. A second research line focuses on patient information and consent procedures, and return of results from research using human materials. This directly relates to the first research line as increasingly studies generate genetic information about hereditary variants. Arne N. Kousholt I work as a postdoc in the lab of Jos Jonkers. My research projects include developing mouse models to functionally investigate BRIP1 as a tumour suppressor for breast cancer, and test treatment strategies for BRIP1 deficient tumours using these mouse models. Moreover, I am working on setting up crispr-cas9 based in-vitro assays to identify pathogenic BRIP1 germline variants. These variants have been identified in high-risk breast cancer families by large scale sequencing efforts. Jos Jonkers The focus of my research is on the genetic dissection of human breast cancer through the use of genetically engineered mouse models (GEMMs) and patient-derived xenograft (PDX) models. My group has generated several mouse models for BRCA1/2-associated hereditary breast cancer and E cadherin-mutated invasive lobular breast cancer. These models are used for both basic and translational studies focusing on genotype-phenotype correlations; discovery and validation of cancer genes and drug targets; tumor-host interactions; and mechanisms of therapy response and resistance. Haico van Attikum We study how cells repair DNA damage in the context of chromatin and use our expertise to development assays for the functional analysis of sequence variants in cancer. Peter Bouwman The focus of my research is on hereditary breast cancer, with special emphasis on the suppressor gene BRCA1. Together with my co-workers in the group of Jos Jonkers, I have generated several novel mouse models for BRCA1 associated tumorigenesis and used these to get more insight in the function of BRCA1 in tumor suppression and treatment response. Currently, I am focusing on the functional classification of BRCA1 sequence variants of unknown clinical significance.

5 Sabine Linn The Linn lab focuses on the development of prognostic and predictive markers for breast and ovarian cancer to guide systemic therapy decisions. Maaike Vreeswijk Our research is focused on the DNA damage response and the translation towards clinical applications. We have developed tools for the reliable assessment of the clinical significance of Variants of Uncertain Significance in breast and ovarian cancer susceptibility genes.

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