Cancer Predisposition

November 8th - 11th, 2018

Co-Chairs:
John M. Maris, MD, University of Pennsylvania, Philadelphia, PA
Judy E. Garber, MD, MPH, Harvard University, Boston, MA

Participants:
Stephen Chanock, MD, National Cancer Institute, Rockville, MD
Olivier DeLattre, Institut Curie, Paris, France
Douglas Easton, PhD, University of Cambridge, Cambridge, United Kingdom
Elizabeth Jaffee, MD, Johns Hopkins University, Baltimore, MD
Allison W. Kurian, MD, M.Sc., Stanford University, Stanford, CA
Mignon Loh, UCSF Benioff Children's Hospital, San Francisco, CA
David Malkin, MD FRCPC FAAP, The Hospital for Sick Children, Toronto, Ontario
Yael Mosse, MD, Children's Hospital of Philadelphia, Philadelphia, PA
Kenneth Offit, MD, Memorial Sloan Kettering Cancer Center, New York, NY
Sharon Plon, MD, PhD, Baylor College of Medicine, Houston, TX
Joshua B. Rubin, MD, PhD, Washington University, St. Louis, MO
Uri Tabori, MD, The Hospital for Sick Children, Toronto, Canada


Program Description

There has been an exponential increase in our discovery of heritable DNA variants that predispose to cancer, but we still have only a rudimentary understanding of the mechanistic underpinnings of cancer initiation and epistatic interactions. We also know that that cancer predisposing events shape the somatic genome, and that genetic, epigenetic and/or stochastic events often select for oncogenic drivers that initiate tumorigenesis. Finally, we have catalogued the majority of cancer predisposing mutations in protein coding genes, but are only at the beginning of understanding how both common and rare DNA variation in the noncoding genome influence malignant transformation and clonal evolution.

The 34th annual Forbeck Foundation meeting will bring together leaders in the field of cancer predisposition, with scientists having expertise in both pediatric and/or adult malignancies. We will review the landscape of what is known about cancer predisposition, but highlight current gaps including understanding polygenic risk and epistatic interaction at the cellular level. We will highlight ongoing efforts to understand the translatable lessons from large association studies on risk prediction and consider the implications of germline mutations for various mechanisms of therapeutic interventions, including immune modulation. We will ask questions such as: "How do we define the spectrum of tumors, adult and pediatric, associated with germline mutations?" and "How much heritability is yet to be discovered?". But we will also delve into cellular mechanisms of tumor initiation, as well as practical issues of variant curation and genetic counseling. Finally, we will attempt to define research priorities and short- and long-term milestones for the cancer predisposition field moving forward.

The 2018 Forum on Cancer Predisposition will be chaired by Dr. John Maris from the Children's Hospital of Philadelphia and the University of Pennsylvania, and Dr. Judy Garber from the Dana Farber Cancer Institute and Harvard Medical School. While we expect to explore mechanisms of cancer initiation in great depth, the meeting will also seek to focus on how research in the field of cancer predisposition should impact patient care now and in the future.