Glioblastoma

Study findings from University of California provide new insights into DNA research

"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 a. 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," wrote D. Yin and colleagues, University of California.

The researchers concluded: "Taken together, these results suggest that this technique is a rapid, robust, and inexpensive method to profile genome-wide abnormalities in GBM. (Mol Cancer Res 2009;7(5):665-77)."

Yin and colleagues published their study in Molecular Cancer Research (High-Resolution Genomic Copy Number Profiling of Glioblastoma Multiforme by Single Nucleotide Polymorphism DNA Microarray. Molecular Cancer Research, 2009;7(5):665-677).

For more information, contact D. Yin, University of California, School Medical, Cedars Sinai Med Center, Division Hematology & Oncology, Davis Bldg 5022 Room, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.

Publisher contact information for the journal Molecular Cancer Research is: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.

Keywords: United States, Los Angeles, Angiogenesis, Biotechnology, Brain Cancer, Brain Carcinoma, Cancer Research, DNA, DNA Microarray, DNA Research, Enzyme Research, Glioblastoma, Kinase, Medical Device, Oncology, VEGF, Vascular Endothelial Growth Factor, University of California.

This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2009, Pain & Central Nervous System Week via NewsRx.com.