PMID- 22157621
OWN - NLM
STAT- MEDLINE
DCOM- 20120213
LR  - 20211021
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 71
IP  - 1
DP  - 2012 Jan
TI  - Clinical stratification of glioblastoma based on alterations in retinoblastoma 
      tumor suppressor protein (RB1) and association with the proneural subtype.
PG  - 83-9
LID - 10.1097/NEN.0b013e31823fe8f1 [doi]
AB  - 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.
FAU - Goldhoff, Patricia
AU  - Goldhoff P
AD  - Division of Neuropathology, Department of Pathology, University of California, 
      San Francisco, San Francisco, California 94143, USA.
FAU - Clarke, Jennifer
AU  - Clarke J
FAU - Smirnov, Ivan
AU  - Smirnov I
FAU - Berger, Mitchel S
AU  - Berger MS
FAU - Prados, Michael D
AU  - Prados MD
FAU - James, C David
AU  - James CD
FAU - Perry, Arie
AU  - Perry A
FAU - Phillips, Joanna J
AU  - Phillips JJ
LA  - eng
GR  - K08 NS063456/NS/NINDS NIH HHS/United States
GR  - K08 NS063456-03/NS/NINDS NIH HHS/United States
GR  - R01 CA159467/CA/NCI NIH HHS/United States
GR  - P50 CA097257/CA/NCI NIH HHS/United States
GR  - P50CA097257/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Retinoblastoma Protein)
SB  - IM
MH  - Brain Neoplasms/*genetics/pathology
MH  - Genetic Association Studies/methods
MH  - Glioblastoma/*genetics/pathology
MH  - Humans
MH  - Neurons/pathology
MH  - Retinoblastoma/*genetics/pathology
MH  - Retinoblastoma Protein/*genetics
MH  - Stem Cells/pathology
PMC - PMC3246124
MID - NIHMS342101
EDAT- 2011/12/14 06:00
MHDA- 2012/02/14 06:00
PMCR- 2013/01/01
CRDT- 2011/12/14 06:00
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2012/02/14 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.1097/NEN.0b013e31823fe8f1 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2012 Jan;71(1):83-9. doi: 10.1097/NEN.0b013e31823fe8f1.