Speakers SESSION 1 Clinical status and perspectives for hereditary - PDF document

Speakers SESSION 1 — Clinical status and perspectives for hereditary breast and ovarian cancer (HBOC) risk prediction. Fergus Couch Text to be added Mayo Clinic Cancer Center and the Center for Individual- ized Medicine, USA Professor Eccles is the Head of the Cancer Sciences Academic Unit Diana Eccles which incorporates the Southampton Cancer Research UK Centre, the University of Southampton, Southampton Clinical Trials Unit and links closely through our clinical Southampton, UK 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 difgerent genetic conditions that predispose to tumour development in families. Fam. Breast and Ovarian Cancer Rita Schmutzler University Hospital Cologne, Germany Tie Linn lab focuses on the development of prognostic and predic- Sabine Linn tive markers for breast and ovarian cancer to guide systemic therapy The Netherlands Cancer decisions. Institute, The Netherlands SESSION 2 — Identifjcation of novel HBOC genes and variants My team is investigating genome maintenance pathways including their Claus Storgaard Sørensen close links with cell proliferation control. We are particularly interested Biotech Research & Inno- in familial breast and ovarian cancer where we focus on factors and vation Center, University of mechanisms that limit tumorigenesis. Copenhagen, Denmark I am fascinated by genetics, and how small genetic difgerences leads to Bjarni Jóhann Vilhjálmsson phenotypic diversity that shapes our lives. Fueled by curiosity, I have Center for Bioinformatics spent my research career on developing statistical methods for under- (BiRC), University of Aarhus, standing the genetic architecture of traits and diseases. Tiis includes Denmark methods for detecting genetic associations in genome-wide association studies, and more recently, polygenic trait prediction and genetic disease risk assessment. Modeling of breast cancer using nongermline mouse model approaches. Stefano Annunziato The Netherlands Cancer Institute, The Netherlands

SESSION 3 — Analysis of the efgects of HBOC gene variants on treatment response. Our laboratory has developed and/or established powerful assay Lisa Wiesmüller systems for the quantitative and qualitative analysis of DSB repair, University Hospital Ulm, recombination and replication stress response mechanisms in immor- Germany talized and primary cells from difgerent organs. Identifjcation of response biomarkers to targeted therapy using PDX Violeta Serra models of breast cancer. Vall d’Hebron Institute of Oncology, Spain Tie main focus of my research is establishing new platforms for study- Oded Kopper ing ovarian cancer. Hubrecht Institute, We are developing 3D culture systems that will support long-term The Netherlands 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 difgerent genes and pathways in the development of HGSOC. SESSION 4 — Model systems and assays for the functional classifjcation of HBOC gene variants. At Bio-Prodict we design and build information systems for protein Bas Vroling (super)families, tailored towards fundamental and applied research Bio-Prodict, in Protein Engineering and DNA Diagnostics. Tiese systems contain The Netherlands 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 efgect of nsSNPs on protein function. Developing in vivo and in vitro crispr-Cas9 approaches. Joey Riepsaame Sir William Dunn School of Pathology, University of Oxford, UK. Tie development of tools and solutions to facilitate Genome Editing. Michel Cannieux Tiis includes development of efgectors (Cas9 variants & Cas9 alterna- Integrated DNA Technologies, tives, and RNA triggers), controls, detection and visualization systems USA (fmuorescence, PCR, NGS). We are interested in the role of germline and somatic genetic factors in- Alvaro NA Monteiro volved in cancer predisposition, initiation, progression, and response to Moffjtt Cancer Center, therapy. Our focus has been on four cancer sites: lung, brain, breast, and USA ovary. Tie overarching theme across these cancer sites is the systems bi- ology approaches and genetics to perform in-depth studies with a view to develop translational solutions to cancer therapy and prevention.

Tie focus of my research is on hereditary breast cancer, with special Peter Bouwman emphasis on the suppressor gene BRCA1. Together with my co-work- The Netherlands Cancer ers in the group of Jos Jonkers, I have generated several novel mouse Institute, The Netherlands models for BRCA1 associated tumorigenesis and used these to get more insight in the function of BRCA1 in tumor suppression and treat- ment response. Currently, I am focusing on the functional classifjcation of BRCA1 sequence variants of unknown clinical signifjcance. Our research is focused on the DNA damage response and the trans- Maaike Vreeswijk lation towards clinical applications. We have developed tools for the Dept.of Human Genetics, reliable assessment of the clinical signifjcance of Variants of Uncertain University Medical Center, Signifjcance in breast and ovarian cancer susceptibility genes. The Netherlands We study how cells repair DNA damage in the context of chromatin Haico van Attikum and use our expertise to development assays for the functional analysis Dept. of Human Genetics, of sequence variants in cancer. Leiden University, The Netherlands Sean Tavtigian Text to be added Huntsman Cancer Institute, University of Utah, USA SESSION 5 — Novel insights in HBOC suppression and consequences for functional assays. Over the past decade, the overarching goal of our laboratory has Shyam Sharan been to understand the functional signifjcance of human BRCA1 and Center for Advanced Pre- BRCA2 variants of unknown clinical signifjcance (VUS). We have clinical Research, National used a mouse embryonic stem (ES) cells-based assay developed in Cancer Institute, USA our laboratory. Desired variants are generated in the human BRCA1 or BRCA2 gene in bacterial artifjcial chromosomes (BAC) using recombineering technology. Tiese are then introduced into ES cells engineered to express a conditional-selectable allele of BRCA1 or BRCA2. Tie extent to which specifjc variants complement the lethality of ES cells with BRCA1 or BRCA2 defjciency 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 signifjcance of our fjndings, we are also engaged in generation of new mouse models. Tiese models serve as power powerful tools that have improved our understanding of the efgect of these variants on growth and development, hematopoiesis, fertility and tumorigenesis. Ralph Scully Text to be added Beth Israel Deaconess Medical Center, Harvard University, USA Using mouse models and a combination of single molecule, cell Arnab Ray Chaudhuri biological and biochemical approaches, we investigate the mechanisms National Cancer Institute, underlying stability of the DNA replication process and its contribution USA 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.