PMID- 21931021
OWN - NLM
STAT- MEDLINE
DCOM- 20111207
LR  - 20211020
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 29
IP  - 30
DP  - 2011 Oct 20
TI  - Genome-wide analyses identify recurrent amplifications of receptor tyrosine 
      kinases and cell-cycle regulatory genes in diffuse intrinsic pontine glioma.
PG  - 3999-4006
LID - 10.1200/JCO.2011.35.5677 [doi]
AB  - PURPOSE: Long-term survival for children with diffuse intrinsic pontine glioma 
      (DIPG) is less than 10%, and new therapeutic targets are urgently required. We 
      evaluated a large cohort of DIPGs to identify recurrent genomic abnormalities and 
      gene expression signatures underlying DIPG. PATIENTS AND METHODS: 
      Single-nucleotide polymorphism arrays were used to compare the frequencies of 
      genomic copy number abnormalities in 43 DIPGs and eight low-grade brainstem 
      gliomas with data from adult and pediatric (non-DIPG) glioblastomas, and 
      expression profiles were evaluated using gene expression arrays for 27 DIPGs, six 
      low-grade brainstem gliomas, and 66 nonbrainstem low-grade gliomas. RESULTS: 
      Frequencies of specific large-scale and focal imbalances varied significantly 
      between DIPGs and nonbrainstem pediatric glioblastomas. Focal amplifications of 
      genes within the receptor tyrosine kinase-Ras-phosphoinositide 3-kinase signaling 
      pathway were found in 47% of DIPGs, the most common of which involved PDGFRA and 
      MET. Thirty percent of DIPGs contained focal amplifications of cell-cycle 
      regulatory genes controlling retinoblastoma protein (RB) phosphorylation, and 21% 
      had concurrent amplification of genes from both pathways. Some tumors showed 
      heterogeneity in amplification patterns. DIPGs showed distinct gene expression 
      signatures related to developmental processes compared with nonbrainstem 
      pediatric high-grade gliomas, whereas expression signatures of low-grade 
      brainstem and nonbrainstem gliomas were similar. CONCLUSION: DIPGs comprise a 
      molecularly related but distinct subgroup of pediatric gliomas. Genomic studies 
      suggest that targeted inhibition of receptor tyrosine kinases and RB regulatory 
      proteins may be useful therapies for DIPG.
FAU - Paugh, Barbara S
AU  - Paugh BS
AD  - St Jude Children's Research Hospital, Memphis, TN 38105, USA.
FAU - Broniscer, Alberto
AU  - Broniscer A
FAU - Qu, Chunxu
AU  - Qu C
FAU - Miller, Claudia P
AU  - Miller CP
FAU - Zhang, Junyuan
AU  - Zhang J
FAU - Tatevossian, Ruth G
AU  - Tatevossian RG
FAU - Olson, James M
AU  - Olson JM
FAU - Geyer, J Russell
AU  - Geyer JR
FAU - Chi, Susan N
AU  - Chi SN
FAU - da Silva, Nasjla Saba
AU  - da Silva NS
FAU - Onar-Thomas, Arzu
AU  - Onar-Thomas A
FAU - Baker, Justin N
AU  - Baker JN
FAU - Gajjar, Amar
AU  - Gajjar A
FAU - Ellison, David W
AU  - Ellison DW
FAU - Baker, Suzanne J
AU  - Baker SJ
LA  - eng
GR  - P01 CA096832/CA/NCI NIH HHS/United States
GR  - R01 CA135554/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110919
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
CIN - J Clin Oncol. 2011 Oct 20;29(30):3956-7. PMID: 21931033
MH  - Adult
MH  - Brain Stem Neoplasms/enzymology/*genetics/pathology
MH  - Cell Cycle Proteins/*genetics
MH  - Child
MH  - Gene Amplification
MH  - Gene Dosage
MH  - Gene Expression Profiling
MH  - *Genes, cdc
MH  - Genome-Wide Association Study
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Polymorphism, Single Nucleotide
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Retinoblastoma Protein/genetics
PMC - PMC3209696
COIS- Authors' disclosures of potential conflicts of interest and author contributions 
      are found at the end of this article.
EDAT- 2011/09/21 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/10/20
CRDT- 2011/09/21 06:00
PHST- 2011/09/21 06:00 [entrez]
PHST- 2011/09/21 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/10/20 00:00 [pmc-release]
AID - JCO.2011.35.5677 [pii]
AID - 55677 [pii]
AID - 10.1200/JCO.2011.35.5677 [doi]
PST - ppublish
SO  - J Clin Oncol. 2011 Oct 20;29(30):3999-4006. doi: 10.1200/JCO.2011.35.5677. Epub 
      2011 Sep 19.