Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity for mutations in clinically relevant genes

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

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background: The 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. Results: We 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. Conclusions: Our 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.

Original languageEnglish (US)
Article number530
JournalGenome Biology
Volume15
Issue number12
DOIs
StatePublished - Dec 3 2014
Externally publishedYes

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High-Throughput Nucleotide Sequencing
neuroglia
tumor
Neuroglia
mutation
Mutation
neoplasms
Point Mutation
gene
Genes
point mutation
amplification
Neoplasms
Glioblastoma
genes
cancer
Oligodendroglioma
Molecular Probes
Genetic Heterogeneity
Gene Amplification

ASJC Scopus subject areas

  • Cell Biology
  • Ecology, Evolution, Behavior and Systematics
  • Genetics

Cite this

Kumar, A., Boyle, E. A., Tokita, M., Mikheev, A. M., Sanger, M. C., Girard, E., ... Shendure, J. (2014). Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity for mutations in clinically relevant genes. Genome Biology, 15(12), [530]. https://doi.org/10.1186/s13059-014-0530-z

Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity for mutations in clinically relevant genes. / Kumar, Akash; Boyle, Evan A.; Tokita, Mari; Mikheev, Andrei M.; Sanger, Michelle C.; Girard, Emily; Silber, John R.; Gonzalez-Cuyar, Luis F.; Hiatt, Joseph B.; Adey, Andrew; Lee, Choli; Kitzman, Jacob O.; Born, Donald E.; Silbergeld, Daniel L.; Olson, James M.; Rostomily, Robert C.; Shendure, Jay.

In: Genome Biology, Vol. 15, No. 12, 530, 03.12.2014.

Research output: Contribution to journalArticle

Kumar, A, Boyle, EA, Tokita, M, Mikheev, AM, Sanger, MC, Girard, E, Silber, JR, Gonzalez-Cuyar, LF, Hiatt, JB, Adey, A, Lee, C, Kitzman, JO, Born, DE, Silbergeld, DL, Olson, JM, Rostomily, RC & Shendure, J 2014, 'Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity for mutations in clinically relevant genes', Genome Biology, vol. 15, no. 12, 530. https://doi.org/10.1186/s13059-014-0530-z
Kumar, Akash ; Boyle, Evan A. ; Tokita, Mari ; Mikheev, Andrei M. ; Sanger, Michelle C. ; Girard, Emily ; Silber, John R. ; Gonzalez-Cuyar, Luis F. ; Hiatt, Joseph B. ; Adey, Andrew ; Lee, Choli ; Kitzman, Jacob O. ; Born, Donald E. ; Silbergeld, Daniel L. ; Olson, James M. ; Rostomily, Robert C. ; Shendure, Jay. / Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity for mutations in clinically relevant genes. In: Genome Biology. 2014 ; Vol. 15, No. 12.
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