Annual Forum 2003 – DNA Damage & Cancer Susceptibility Syndromes

Co-Chairs:
Alan D’Andrea, MD, Dana Farber Cancer Institute, Boston, MA
Jan Hoeijmakers, Erasmus University, Rotterdam, The Netherlands

Participants:
Philip C. Hanawalt, Stanford University, Stanford, CA
Ian Hickson, Ph.D., Oxford Cancer Centre, Oxford, England
Steve Jackson, Ph.D., University of Cambridge, Cambridge, England
Hans Joenje, Ph.D., VU University Medical Centre, Amsterdam, The Netherlands
Michael Kastan, MD, Ph.D., St Jude Children’s Research Hospital, Memphis, TN
Richard D. Kolodner, Ph.D., University of California, San Diego, La Jolla, CA
Tom A. Kunkel, National Inst. of Health, Research Triangle Park, NC
John H. J. Petrini, Ph.D., Memorial Sloan-Kettering Cancer Center, New York, NY
Gregory L. Verdine, Harvard University, Cambridge, MA
Jean Y. Wang, Ph.D., University of California, San Diego, La Jolla, CA
Stephen West, Ph.D., Cancer Research UK, Herts, England
Sam Wilson, National Inst. of Health, Research Triangle Park, NC
Richard D. Wood, Ph.D., FRS, Univ. of Pittsburgh Cancer Inst, Pittsburgh, PA
Michael B. Yaffe, MD, Ph.D., Massachusetts Inst. of Technology. Cambridge, MA


Layout and Goals
Sessions:

  1. DNA Repair I
  2. Damage Response & Checkpoints
  3. DNA Repair II
  4. Chromosome Instability

The important role that DNA damage plays in cancer development is illustrated by the clear connections between exposures to certain types of DNA damaging agents in the environment and the development of cancer, such as the links between cigarette smoking and lung cancer or sunlight exposure and skin cancer. In addition, the majority of inherited syndromes characterized to date that lead to increased cancer development in families result from inherited mutations in genes that are important for DNA damage responses. For example, inherited mutations in either the Brca1 or p53 genes results in a very high risk of developing breast cancer and both of these gene products are important for helping cells respond to various types of DNA damage. The genes mutated in certain rare diseases that affect children, such as Fanconi's Anemia, Ataxia-telangiectasia, and Xeroderma Pigmentosum, all play roles in cellular responses to DNA damage and children with these diseases have very high incidences of certain cancers. Studies of the genes mutated in these diseases have led to a much better understanding of how all cells respond to DNA damage and even more importantly to insights about how cancers develop. In addition, since radiation therapy and most chemotherapy used to treat cancer actually cause DNA damage, understanding how these gene products operate provides new ways to approach the treatment of cancer. The discussions at the forum will focus on how these gene products function, contribute to cancer and can be manipulated to improve cancer therapies.


Outcome Report
The important role that DNA damage plays in cancer development is illustrated by the clear connections between exposures to certain types of DNA damaging agents in the environment and the development of cancer, such as the links between cigarette smoking and lung cancer or sunlight exposure and skin cancer. In addition, the majority of inherited syndromes characterized to date that lead to increased cancer development in families result from inherited mutations in genes that are important for DNA damage responses. For example, inherited mutations in either the Brca1 or p53 genes results in a very high risk of developing breast cancer and both of these gene products are important for helping cells respond to various types of DNA damage. The genes mutated in certain rare diseases that affect children, such as Fanconi’s Anemia, Ataxia-telangiectasia, and Xeroderma Pigmentosum, all play roles in cellular responses to DNA damage and children with these diseases have very high incidences of certain cancers. Studies of the genes mutated in these diseases have led to a much better understanding of how all cells respond to DNA damage and even more importantly to insights about how cancers develop. In addition, since radiation therapy and most chemotherapy used to treat cancer actually cause DNA damage, understanding how these gene products operate provides new ways to approach the treatment of cancer. The discussions at the forum will focus on how these gene products function, how they contribute to cancer development, and how they can be manipulated to improve cancer therapies.