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SUMMARY:The Cancer Genome Atlas: oncogenic signature classes and the desig
 n of combinatorial therapy - Chris Sander (MSKCC)
DTSTART:20140613T110000Z
DTEND:20140613T120000Z
UID:TALK52845@talks.cam.ac.uk
CONTACT:Florian Markowetz
DESCRIPTION:Cancer therapy is challenged by the diversity of molecular imp
 lementations of oncogenic processes and by the resulting variation in ther
 apeutic responses. Projects such as The Cancer Genome Atlas (TCGA) provide
  molecular tumor maps in unprecedented detail. The interpretation of these
  maps remains a major challenge. We have distilled thousands of genetic an
 d epigenetic features altered in cancers to just a few hundred selected fu
 nctional events (SFEs). Using this simplified description\, we derived a h
 ierarchical classification of thousands TCGA tumors from diverse cancer ty
 pes. The top classes are dominated by either mutations (M class) or copy n
 umber changes (C class). This distinction is clearest at the extremes of g
 enomic instability\, indicating the presence of different oncogenic proces
 ses. The full hierarchy shows functional event patterns characteristic of 
 multiple cross-tissue groups of tumors\, termed oncogenic signature (OncoS
 ign) classes. Targetable functional events in a tumor class are suggestive
  of class-specific combination therapy. These results may assist in the de
 finition of clinical trials to match actionable oncogenic signatures with 
 personalized therapies. I will also review our perturbation biology approa
 ch to the design of combinatorial therapy to overcome the emergence of res
 istance to targeted therapeutics\, such as the RAF inhibitor in melanoma.
LOCATION:CRUK CI Room 215
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