Identification of noninvasive imaging surrogates for brain tumor gene-expression modules.
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.
Diehn
Maximilian
M
Department of Radiology, University of California San Diego Medical Center, San Diego, CA 92103, USA.
Nardini
Christine
C
Wang
David S
DS
McGovern
Susan
S
Jayaraman
Mahesh
M
Liang
Yu
Y
Aldape
Kenneth
K
Cha
Soonmee
S
Kuo
Michael D
MD
D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D019411:Clinical Laboratory Techniques; D066246:ErbB Receptors / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009361:Neoplasm Invasiveness; D010641:Phenotype; D015996:Survival Rate; D016896:Treatment Outcome
D066246:ErbB Receptors