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Comprehensive genomic characterization defines human glioblastoma genes and core pathways

(2008) NATURE. 455(7216). p.1061-1068
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Abstract
Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
Keywords
HIGH-FREQUENCY, PIK3CA GENE, ALKYLATING-AGENTS, MALIGNANT GLIOMAS, SOMATIC MUTATIONS, NEUROFIBROMATOSIS TYPE-1, MISMATCH REPAIR, NF1 GENE, CELL-LINES, TUMORS

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Citation

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Chicago
Chin, L, M Meyerson, K Aldape, D Bigner, T Mikkelsen, S VandenBerg, A Kahn, et al. 2008. “Comprehensive Genomic Characterization Defines Human Glioblastoma Genes and Core Pathways.” Nature 455 (7216): 1061–1068.
APA
Chin, L., Meyerson, M., Aldape, K., Bigner, D., Mikkelsen, T., VandenBerg, S., Kahn, A., et al. (2008). Comprehensive genomic characterization defines human glioblastoma genes and core pathways. NATURE, 455(7216), 1061–1068.
Vancouver
1.
Chin L, Meyerson M, Aldape K, Bigner D, Mikkelsen T, VandenBerg S, et al. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. NATURE. 2008;455(7216):1061–8.
MLA
Chin, L, M Meyerson, K Aldape, et al. “Comprehensive Genomic Characterization Defines Human Glioblastoma Genes and Core Pathways.” NATURE 455.7216 (2008): 1061–1068. Print.
@article{1053670,
  abstract     = {Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.},
  author       = {Chin, L and Meyerson, M and Aldape, K and Bigner, D and Mikkelsen, T and VandenBerg, S and Kahn, A and Penny, R and Ferguson, ML and Gerhard, DS and Getz, G and Brennan, C and Taylor, BS and Winckler, W and Park, P and Ladanyi, M and Hoadley, KA and Verhaak, RGW and Hayes, DN and Spellman, Paul T and Absher, D and Weir, BA and Ding, L and Wheeler, D and Lawrence, MS and Cibulskis, K and Mardis, E and Zhang, JingHui and Wilson, RK and Donehower, L and Wheeler, DA and Purdom, E and Wallis, J and Laird, PW and Herman, JG and Schuebel, KE and Weisenberger, DJ and Baylin, SB and Schultz, N and Yao, J and Wiedemeyer, R and Weinstein, J and Sander, C and Gibbs, RA and Gray, J and Kucherlapati, R and Lander, ES and Myers, RM and Perou, CM and McLendon, Roger and Friedman, Allan and Van Meir, Erwin G and Brat, Daniel J and Mastrogianakis, Gena Marie and Olson, Jeffrey J and Lehman, Norman and Yung, WK Alfred and Bogler, Oliver and Berger, Mitchel and Prados, Michael and Muzny, Donna and Morgan, Margaret and Scherer, Steve and Sabo, Aniko and Nazareth, Lynn and Lewis, Lora and Hall, Otis and Zhu, YiMing and Ren, YanRu and Alvi, Omar and Yao, JiQiang and Hawes, Alicia and Jhangiani, Shalini and Fowler, Gerald and San Lucas, Anthony and Kovar, Christie and Cree, Andrew and Dinh, Huyen and Santibanez, Jireh and Joshi, Vandita and Gonzalez-Garay, Manuel L and Miller, Christopher A and Milosavljevic, Aleksandar and Sougnez, Carrie and Fennell, Tim and Mahan, Scott and Wilkinson, Jane and Ziaugra, Liuda and Onofrio, Robert and Bloom, Toby and Nicol, Rob and Ardlie, Kristin and Baldwin, Jennifer and Gabriel, Stacey and Fulton, Robert S and McLellan, Michael D and Larson, David E and Shi, XiaoQi and Abbott, Rachel and Fulton, Lucinda and Chen, Ken and Koboldt, Daniel C and Wendl, Michael C and Meyer, Rick and Tang, YuZhu and Lin, Ling and Osborne, John R and Dunford-Shore, Brian H and Miner, Tracie L and Delehaunty, Kim and Markovic, Chris and Swift, Gary and Courtney, William and Pohl, Craig and Abbott, Scott and Hawkins, Amy and Leong, Shin and Haipek, Carrie and Schmidt, Heather and Wiechert, Maddy and Vickery, Tammi and Scott, Sacha and Dooling, David J and Chinwalla, Asif and Weinstock, George M and O'Kelly, Michael and Robinson, Jim and Alexe, Gabriele and Beroukhim, Rameen and Carter, Scott and Chiang, Derek and Gould, Josh and Gupta, Supriya and Korn, Josh and Mermel, Craig and Mesirov, Jill and Monti, Stefano and Nguyen, Huy and Parkin, Melissa and Reich, Michael and Stransky, Nicolas and Garraway, Levi and Golub, Todd and Protopopov, Alexei and Perna, Ilana and Aronson, Sandy and Sathiamoorthy, Narayan and Ren, Georgia and Kim, Hyunsoo and Kong, Sek Won and Xiao, YongHong and Kohane, Isaac S and Seidman, Jon and Cope, Leslie and Pan, Fei and Van Den Berg, David and Van Neste, Leander and Yi, Joo Mi and Li, Jun Z and Southwick, Audrey and Brady, Shannon and Aggarwal, Amita and Chung, Tisha and Sherlock, Gavin and Brooks, James D and Jakkula, Lakshmi R and Lapuk, Anna V and Marr, Henry and Dorton, Shannon and Choi, Yoon Gi and Han, Ju and Ray, Amrita and Wang, Victoria and Durinck, Steffen and Robinson, Mark and Wang, Nicholas J and Vranizan, Karen and Peng, Vivian and Van Name, Eric and Fontenay, Gerald V and Ngai, John and Conboy, John G and Parvin, Bahram and Feiler, Heidi S and Speed, Terence P and Socci, Nicholas D and Olshen, Adam and Lash, Alex and Reva, Boris and Antipin, Yevgeniy and Stukalov, Alexey and Gross, Benjamin and Cerami, Ethan and Wang, Wei Qing and Qin, Li-Xuan and Seshan, Venkatraman E and Villafania, Liliana and Cavatore, Magali and Borsu, Laetitia and Viale, Agnes and Gerald, William and Topal, Michael D and Qi, Yuan and Balu, Sai and Shi, Yan and Wu, George and Bittner, Michael and Shelton, Troy and Lenkiewicz, Elizabeth and Morris, Scott and Beasley, Debbie and Sanders, Sheri and Sfeir, Robert and Chen, Jessica and Nassau, David and Feng, Larry and Hickey, Erin and Schaefer, Carl and Madhavan, Subha and Buetow, Ken and Barker, Anna and Vockley, Joseph and Compton, Carolyn and Vaught, Jim and Fielding, Peter and Collins, Francis and Good, Peter and Guyer, Mark and Ozenberger, Brad and Peterson, Jane and Thomson, Elizabeth},
  issn         = {0028-0836},
  journal      = {NATURE},
  keyword      = {HIGH-FREQUENCY,PIK3CA GENE,ALKYLATING-AGENTS,MALIGNANT GLIOMAS,SOMATIC MUTATIONS,NEUROFIBROMATOSIS TYPE-1,MISMATCH REPAIR,NF1 GENE,CELL-LINES,TUMORS},
  language     = {eng},
  number       = {7216},
  pages        = {1061--1068},
  title        = {Comprehensive genomic characterization defines human glioblastoma genes and core pathways},
  url          = {http://dx.doi.org/10.1038/nature07385},
  volume       = {455},
  year         = {2008},
}

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