RGD Reference Report - Clinical stratification of glioblastoma based on alterations in retinoblastoma tumor suppressor protein (RB1) and association with the proneural subtype.

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Clinical stratification of glioblastoma based on alterations in retinoblastoma tumor suppressor protein (RB1) and association with the proneural subtype.
Authors:	Goldhoff, Patricia Clarke, Jennifer Smirnov, Ivan Berger, Mitchel S Prados, Michael D James, C David Perry, Arie Phillips, Joanna J
Citation:	Goldhoff P, etal., J Neuropathol Exp Neurol. 2012 Jan;71(1):83-9. doi: 10.1097/NEN.0b013e31823fe8f1.
RGD ID:	13782062
Pubmed:	PMID:22157621 (View Abstract at PubMed)
PMCID:	PMC3246124 (View Article at PubMed Central)
DOI:	DOI:10.1097/NEN.0b013e31823fe8f1 (Journal Full-text)
A recent study of CDK4/6 inhibitors in glioblastoma (GBM) xenografts identified retinoblastoma tumor suppressor protein RB1 status as a determinant of tumor therapeutic efficacy. Because of the need for clinically applicable RB1 testing, we assessed the utility of 2 complementary methods for determining RB1 status in GBM. Using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), we analyzed 34 GBMs that had also undergone molecular characterization as part of The Cancer Genome Atlas (TCGA). By IHC, 4 tumors (11.8%) had complete loss of RB protein expression, including 2 with homozygous deletion of RB1 by FISH and 1 with hemizygous deletion of RB1 by FISH combined with a novel nonsense mutation in RB1. Consistent with these results, in an independent set of 51 GBMs tested by IHC, we demonstrated loss of RB1 protein in 5 (9.8%). In GBM molecular subtype analysis of TCGA data, complete loss of RB1 transcript expression was seen in 18 (10.6%) of 170 tumors, and these were highly enriched for, but not exclusive to, the proneural subtype (p < 0.01). These data support the use of IHC for determining RB1 status in clinical GBM specimens and suggest that RB1 alterations may be more common in certain GBM subgroups.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
RB1	Human	glioblastoma proneural subtype		IEP		RNA:decreased expression:brain:	RGD
Rb1	Rat	glioblastoma proneural subtype		ISO	RB1 (Homo sapiens)	RNA:decreased expression:brain:	RGD
Rb1	Mouse	glioblastoma proneural subtype		ISO	RB1 (Homo sapiens)	RNA:decreased expression:brain:	RGD

Objects Annotated

Genes (Rattus norvegicus)

Rb1 (RB transcriptional corepressor 1)

Genes (Mus musculus)

Rb1 (RB transcriptional corepressor 1)

Genes (Homo sapiens)

RB1 (RB transcriptional corepressor 1)

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Clinical stratification of glioblastoma based on alterations in retinoblastoma tumor suppressor protein (RB1) and association with the proneural subtype.