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BIOLOGICAL SCIENCES / MEDICAL SCIENCES
Identification of noninvasive imaging surrogates for brain tumor gene-expression modules
*Department of Radiology and **Center for Translational Medical Systems, University of California San Diego Medical Center, San Diego, CA 92103; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305; Department of Neuropathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; Department of Radiology, Brown University, Providence, RI 02912; ¶Department of Neurological Surgery, Brain Tumor Research Center, University of California San Francisco Medical Center, San Francisco, CA 94143; and ||Department of Radiology, University of California San Francisco Medical Center, San Francisco, CA 94143
Communicated by Helen M. Ranney, University of California at San Diego, La Jolla, CA, February 9, 2008 (received for review October 16, 2007)
Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor in adults. We combined neuroimaging and DNA microarray analysis to create a multidimensional map of gene-expression patterns in GBM that provided clinically relevant insights into tumor biology. Tumor contrast enhancement and mass effect predicted activation of specific hypoxia and proliferation gene-expression programs, respectively. Overexpression of EGFR, a receptor tyrosine kinase and potential therapeutic target, was also directly inferred by neuroimaging and was validated in an independent set of tumors by immunohistochemistry. Furthermore, imaging provided insights into the intratumoral distribution of gene-expression patterns within GBM. Most notably, an "infiltrative" imaging phenotype was identified that predicted patient outcome. Patients with this imaging phenotype had a greater tendency toward having multiple tumor foci and demonstrated significantly shorter survival than their counterparts. Our findings provide an in vivo portrait of genome-wide gene expression in GBM and offer a potential strategy for noninvasively selecting patients who may be candidates for individualized therapies.
cancer | genomics | glioblastoma multiforme | radiogenomics
Author contributions: M.D. and M.D.K. designed research; M.D., C.N., D.S.W., S.M., M.J., Y.L., K.A., S.C., and M.D.K. performed research; C.N. contributed new reagents/analytic tools; M.D., C.N., M.J., and M.D.K. analyzed data; and M.D. and M.D.K. wrote the paper.
Conflict of interest statement: M.D.K. has filed a patent application in an area related to this field of work.
This article contains supporting information online at www.pnas.org/cgi/data/0801279105/DCSupplemental.
To whom correspondence should be addressed. E-mail: mkuo{at}ucsd.edu
© 2008 by The National Academy of Sciences of the USA
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