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Insulin-like
growth factor binding protein 2: gene expression microarrays and the
hypothesis-generation paradigm
Zhang W, Wang H, Song SW, Fuller GN
Department of Pathology, The University of Texas M.D. Anderson Cancer Center,
Houston 77030, USA. wzhang@mdanderson.org
A major goal of modern medicine is to identify key genes and their products that
are altered in the diseased state and to elucidate the molecular mechanisms
underlying disease development, progression, and resistance to therapy.
This is a daunting task given the exceptionally high complexity of the human
genome.
The paradigm for research has historically been hypothesis-driven despite the
fact that the hypotheses under scrutiny often rest on tenuous subjective grounds
or are derived from and dependent on chance observation.
The imminent deciphering of the complete human genome, coupled with recent
advances in high-throughput bioanalytical technology, has made possible a new
paradigm in which data-based hypothesis-generation is the initial step in the
investigative process, followed by hypothesis-testing.
Genomics technologies are the primary source of the new hypothesis-generating
capabilities that are now empowering biomedical researchers.
The synergistic interaction between contemporary genomics technologies and the
hypothesis-generation paradigm is well-illustrated by the discovery and
subsequent ongoing study of the role of insulin-like growth factor binding
protein 2 (IGFBP2) in human glioma biology.
Using gene expression microarray technology, the IGFBP2 gene was recently found
to be highly and differentially overexpressed in the most advanced grade of
human glioma, glioblastoma.
Based on this discovery, subsequent functional studies were initiated that
suggest that IGFBP2 overexpression may contribute to the invasive nature of
glioblastoma, and that IGFBP2 may exert its function via a newly identified
novel binding protein.
The IGFBP2 story is but one example of the power and potential of the new
molecular methodologies that are transforming modern diagnostic and
investigative neuropathology.
PMID:
11770904 [PubMed - indexed for MEDLINE]
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