Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity for mutations in clinically relevant genes |
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Authors: | Akash Kumar Evan A Boyle Mari Tokita Andrei M Mikheev Michelle C Sanger Emily Girard John R Silber Luis F Gonzalez-Cuyar Joseph B Hiatt Andrew Adey Choli Lee Jacob O Kitzman Donald E Born Daniel L Silbergeld James M Olson Robert C Rostomily Jay Shendure |
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Affiliation: | .Department of Genome Sciences, University of Washington, Seattle, WA 98195 USA ;.Division of Medical Genetics, University of Washington, Seattle, WA 98195 USA ;.Department of Neurosurgery, University of Washington, Seattle, WA 98195 USA ;.Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 USA ;.Department of Pathology, University of Washington, Seattle, WA 98195 USA |
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Abstract: | BackgroundThe extent of intratumoral mutational heterogeneity remains unclear in gliomas, the most common primary brain tumors, especially with respect to point mutation. To address this, we applied single molecule molecular inversion probes targeting 33 cancer genes to assay both point mutations and gene amplifications within spatially distinct regions of 14 glial tumors.ResultsWe find evidence of regional mutational heterogeneity in multiple tumors, including mutations in TP53 and RB1 in an anaplastic oligodendroglioma and amplifications in PDGFRA and KIT in two glioblastomas (GBMs). Immunohistochemistry confirms heterogeneity of TP53 mutation and PDGFRA amplification. In all, 3 out of 14 glial tumors surveyed have evidence for heterogeneity for clinically relevant mutations.ConclusionsOur results underscore the need to sample multiple regions in GBM and other glial tumors when devising personalized treatments based on genomic information, and furthermore demonstrate the importance of measuring both point mutation and copy number alteration while investigating genetic heterogeneity within cancer samples.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-014-0530-z) contains supplementary material, which is available to authorized users. |
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