Source:http://linkedlifedata.com/resource/pubmed/id/19435819
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2009-5-21
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| pubmed:abstractText |
Glioblastoma multiforme (GBM) is an extremely malignant brain tumor. To identify new genomic alterations in GBM, genomic DNA of tumor tissue/explants from 55 individuals and 6 GBM cell lines were examined using single nucleotide polymorphism DNA microarray (SNP-Chip). Further gene expression analysis relied on an additional 56 GBM samples. SNP-Chip results were validated using several techniques, including quantitative PCR (Q-PCR), nucleotide sequencing, and a combination of Q-PCR and detection of microsatellite markers for loss of heterozygosity with normal copy number [acquired uniparental disomy (AUPD)]. Whole genomic DNA copy number in each GBM sample was profiled by SNP-Chip. Several signaling pathways were frequently abnormal. Either the p16(INK4A)/p15(INK4B)-CDK4/6-pRb or p14(ARF)-MDM2/4-p53 pathways were abnormal in 89% (49 of 55) of cases. Simultaneous abnormalities of both pathways occurred in 84% (46 of 55) samples. The phosphoinositide 3-kinase pathway was altered in 71% (39 of 55) GBMs either by deletion of PTEN or amplification of epidermal growth factor receptor and/or vascular endothelial growth factor receptor/platelet-derived growth factor receptor alpha. Deletion of chromosome 6q26-27 often occurred (16 of 55 samples). The minimum common deleted region included PARK2, PACRG, QKI, and PDE10A genes. Further reverse transcription Q-PCR studies showed that PARK2 expression was decreased in another collection of GBMs at a frequency of 61% (34 of 56) of samples. The 1p36.23 region was deleted in 35% (19 of 55) of samples. Notably, three samples had homozygous deletion encompassing this site. Also, a novel internal deletion of a putative tumor suppressor gene, LRP1B, was discovered causing an aberrant protein. AUPDs occurred in 58% (32 of 55) of the GBM samples and five of six GBM cell lines. A common AUPD was found at chromosome 17p13.3-12 (included p53 gene) in 13 of 61 samples and cell lines. Single-strand conformational polymorphism and nucleotide sequencing showed that 9 of 13 of these samples had homozygous p53 mutations, suggesting that mitotic recombination duplicated the abnormal p53 gene, probably providing a growth advantage to these cells. A significantly shortened survival time was found in patients with 13q14 (RB) deletion or 17p13.1 (p53) deletion/AUPD. Taken together, these results suggest that this technique is a rapid, robust, and inexpensive method to profile genome-wide abnormalities in GBM.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
|
| pubmed:issn |
1541-7786
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| pubmed:author |
pubmed-author:BlackKeith LKL,
pubmed-author:DugasMartinM,
pubmed-author:EoliMaricaM,
pubmed-author:FinocchiaroGaetanoG,
pubmed-author:HuynhThienT,
pubmed-author:KatoMotohiroM,
pubmed-author:KawamataNorihikoN,
pubmed-author:KoefflerH PhillipHP,
pubmed-author:LewisT WTW,
pubmed-author:LiuGentaoG,
pubmed-author:OgawaSeishiS,
pubmed-author:RuckertChristianC,
pubmed-author:SanadaMasashiM,
pubmed-author:TuniciPatriziaP,
pubmed-author:YinDongD
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| pubmed:issnType |
Print
|
| pubmed:volume |
7
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
665-77
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| pubmed:meshHeading |
pubmed-meshheading:19435819-Adolescent,
pubmed-meshheading:19435819-Adult,
pubmed-meshheading:19435819-Aged,
pubmed-meshheading:19435819-Amino Acid Sequence,
pubmed-meshheading:19435819-Base Sequence,
pubmed-meshheading:19435819-Cell Line, Tumor,
pubmed-meshheading:19435819-Female,
pubmed-meshheading:19435819-Gene Amplification,
pubmed-meshheading:19435819-Gene Dosage,
pubmed-meshheading:19435819-Glioblastoma,
pubmed-meshheading:19435819-Humans,
pubmed-meshheading:19435819-Loss of Heterozygosity,
pubmed-meshheading:19435819-Male,
pubmed-meshheading:19435819-Middle Aged,
pubmed-meshheading:19435819-Models, Biological,
pubmed-meshheading:19435819-Molecular Sequence Data,
pubmed-meshheading:19435819-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:19435819-Polymorphism, Single Nucleotide,
pubmed-meshheading:19435819-Polymorphism, Single-Stranded Conformational,
pubmed-meshheading:19435819-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19435819-Sequence Analysis, DNA,
pubmed-meshheading:19435819-Sequence Deletion,
pubmed-meshheading:19435819-Signal Transduction,
pubmed-meshheading:19435819-Uniparental Disomy,
pubmed-meshheading:19435819-Young Adult
|
| pubmed:year |
2009
|
| pubmed:articleTitle |
High-resolution genomic copy number profiling of glioblastoma multiforme by single nucleotide polymorphism DNA microarray.
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| pubmed:affiliation |
Division of Hematology and Oncology, Cedars-Sinai Medical Center, University of California at Los Angeles School of Medicine, Davis Building 5022 Room, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. Dong.Yin@cshs.org
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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