The End of a Beginning in Personalized Medicine


Dr. Ken Buetow, BIG Health Catalyst

The first manuscript reporting results for The Cancer Genome Atlas (TCGA) was published today in the advanced, on-line addition of Nature.  TCGA is a 3-year pilot project of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) whose goal is to increase our comprehensive understanding of the molecular basis of cancer.  The TCGA team describes the discovery of a complex collection of molecular alterations in glioblastoma multiforme (GBM) that have potential implications for the diagnosis and treatment.  GBM is the most common form of brain cancer in adults affecting 21,000 people annually.

The paper describes previously unknown high frequency mutations for NF1, ERBB2, and PIK3R1 and confirms previous mutational findings in PTEN, RB1, EGFR, and PIKC3A.  It implicates three pathways: the CDK/cyclin/CDK inhibitor/RB pathway, the p53 pathway, and the RTK/RAS/PI3K pathway as the target of molecular alterations in over 80% of GBMs.

These findings, whose true biologic and clinical significance will only be known over time, are of immediate significance in two ways.  First, this novel integration of multidimensional molecular data provides a rare systematic view of cancer.  It is breath taking to see the diversity of molecular mechanisms that generate this single cancer type.  Multiple genes, disrupted by multiple mechanisms (mutations, deletions, amplifications, and epigenetic alterations) interacting through multiple pathways.  However, through this team approach, in a matter of months the cancer community has learned what might have otherwise taken years. What would have been separate observations in different labs in separate papers measuring different molecular dimensions all requiring additional studies to understand the interactions are all seen in concert, simultaneously.  WOW!

Second, but perhaps of greater significance, this multidimensional information is available in an integrated fashion to biomedical community NOW!  By going to the caBIG Cancer Molecular Analysis Portal that integrates and shares the data –, one can examine and judge for one’s self the assertions made in the manuscript.  Alternatively, a researcher can perform their own in-silico experiments.  This first manuscript will likely be the first of many significant finding drawn from this incredibly rich data resource

Of course the real challenge laid bare is how do we translate these findings into next generation interventions?  The BIG Health Consortium’s 21st Century platform for discovery and translation provides one possible solution.

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