The goal of the Cancer Genetics Program is to go beyond the standard genotype-phenotype
correlation toward understanding cross talk between genes and non-genetic influences
on genes. Genes do not act in isolation and these types of interactions impact
the resulting phenotype with profound implications in human cancer.
Highlights
of research by Program investigators include
Jason
Lieb’s development
of method to fractionate chromatin from the yeast Saccharomyces cerevisiae
into functionally distinct genomic regions. Such a method will be applicable
to mammalian cells and it has the potential to be an extremely powerful
new diagnostic /prognostic clinical tool.
Chuck
Perou has demonstrated that
gene
expression-defined cancer subtypes are predictive of overall patient
survival and relapse-free survival in his cohort of patients as well as in
independent
cohorts.
David Threadgill has focused on identification of modifiers
of Egf receptor activity that may be useful for identifying patients that
will
not
respond to anti-Egfr therapy. This work has lead to the development
of a translational project for the GI SPORE application to investigate variation
in response to
Egfr inhibition.
Dr. Terry Magnuson leads the Program and he has made
significant contributions in the area of chromatin remodeling and epigenetics
as well
as novel approaches for functional genomics.
The mouse models of
human cancer group, led by Terry
Van Dyke, has created many opportunities
for
those
studying
cancer etiology and therapy.
Recent recruitment in statistical
and human genetics, as well as computational approaches, are expanding
the scope of
the program,
particularly its impact on the population and clinical sciences.
The recruitment and program leadership of core facility development
and enlargement
is
providing additional opportunities for collaboration and participation
in high priority
NCI initiatives, e.g., systems biology and caBIG. In 2003,
the 22 program
faculty investigators have 51 grants and $10.3 million in total
extramural support.
Peer-reviewed research funding totals 44 grants and $9.8 million,
including 17 grants ($4.1 million) from the National Cancer Institute.
Recognizing that individuals differ in their susceptibility to cancer
based upon
polymorphic
differences in low penetrance cancer genes and that cancers
progress because of accumulation of multiple genetic abnormalities, the
Cancer Genetics
Program
Faculty have outlined five future strategic goals:
High
penetrance
cancer genes in model systems,
Loss of genome integrity
that can lead to uncontrolled
cell growth, invasion and metastasis,
Epigenetics
and the involvement of chromatin organization in regulation of DNA metabolism,
Development
of genome-wide strategies that depend on statistical
tools to
gather genome
information, and
Quantitative genetics to identify
modifier
genes and gene networks.
