You are here

Neuro Oncol DOI:10.1093/neuonc/nos246

Integrative functional genomics identifies RINT1 as a novel GBM oncogene.

Publication TypeJournal Article
Year of Publication2012
AuthorsQuayle, SN, Chheda, MG, Shukla, SA, Wiedemeyer, R, Tamayo, P, Dewan, RW, Zhuang, L, Huang-Hobbs, E, Haidar, S, Xiao, Y, Ligon, KL, Hahn, WC, Chin, L
JournalNeuro Oncol
Date Published2012 Nov
KeywordsAnimals, Brain Neoplasms, Cell Cycle Proteins, Cell Transformation, Neoplastic, Comparative Genomic Hybridization, Genomics, Glioblastoma, Humans, Immunoblotting, Immunohistochemistry, Mice, Mice, Nude, Oncogenes

Large-scale cancer genomics efforts are identifying hundreds of somatic genomic alterations in glioblastoma (GBM). Distinguishing between active driver and neutral passenger alterations requires functional assessment of each gene; therefore, integrating biological weight of evidence with statistical significance for each genomic alteration will enable better prioritization for downstream studies. Here, we demonstrate the feasibility and potential of in vitro functional genomic screens to rapidly and systematically prioritize high-probability candidate genes for in vivo validation. Integration of low-complexity gain- and loss-of-function screens designed on the basis of genomic data identified 6 candidate GBM oncogenes, and RINT1 was validated as a novel GBM oncogene based on its ability to confer tumorigenicity to primary nontransformed murine astrocytes in vivo. Cancer genomics-guided low-complexity genomic screens can quickly provide a functional filter to prioritize high-value targets for further downstream mechanistic and translational studies.


Alternate JournalNeuro-oncology
PubMed ID23074196
PubMed Central IDPMC3480269
Grant ListK08 NS062907 / NS / NINDS NIH HHS / United States
K08NS062907 / NS / NINDS NIH HHS / United States
P01CA095616 / CA / NCI NIH HHS / United States
K12CA090354 / CA / NCI NIH HHS / United States
RC2CA148268 / CA / NCI NIH HHS / United States
U24CA143845 / CA / NCI NIH HHS / United States
U01CA141508 / CA / NCI NIH HHS / United States