Comprehensive genomic characterization defines human glioblastoma genes and core pathways

Roger McLendon, Allan Friedman, Darrell Bigner, Erwin G. Van Meir, Daniel J. Brat, Gena M. Mastrogianakis, Jeffrey J. Olson, Tom Mikkelsen, Norman Lehman, Ken Aldape, W. K Alfred Yung, Oliver Bogler, John N. Weinstein, Scott VandenBerg, Mitchel Berger, Michael Prados, Donna Muzny, Margaret Morgan, Steve Scherer, Aniko SaboLynn Nazareth, Lora Lewis, Otis Hall, Yiming Zhu, Yanru Ren, Omar Alvi, Jiqiang Yao, Alicia Hawes, Shalini Jhangiani, Gerald Fowler, Anthony San Lucas, Christie Kovar, Andrew Cree, Huyen Dinh, Jireh Santibanez, Vandita Joshi, Manuel L. Gonzalez-Garay, Christopher A. Miller, Aleksandar Milosavljevic, Larry Donehower, David A. Wheeler, Richard A. Gibbs, Kristian Cibulskis, Carrie Sougnez, Tim Fennell, Scott Mahan, Jane Wilkinson, Liuda Ziaugra, Robert Onofrio, Toby Bloom, Rob Nicol, Kristin Ardlie, Jennifer Baldwin, Stacey Gabriel, Eric S. Lander, Li Ding, Robert S. Fulton, Michael D. McLellan, John Wallis, David E. Larson, Xiaoqi Shi, Rachel Abbott, Lucinda Fulton, Ken Chen, Daniel C. Koboldt, Michael C. Wendl, Rick Meyer, Yuzhu Tang, Ling Lin, John R. Osborne, Brian H. Dunford-Shore, Tracie L. Miner, Kim Delehaunty, Chris Markovic, Gary Swift, William Courtney, Craig Pohl, Scott Abbott, Amy Hawkins, Shin Leong, Carrie Haipek, Heather Schmidt, Maddy Wiechert, Tammi Vickery, Sacha Scott, David J. Dooling, Asif Chinwalla, George M. Weinstock, Elaine R. Mardis, Richard K. Wilson, Gad Getz, Wendy Winckler, Roel G W Verhaak, Michael S. Lawrence, Michael O'Kelly, Jim Robinson, Gabriele Alexe, Rameen Beroukhim, Scott Carter, Derek Chiang, Josh Gould, Supriya Gupta, Josh Korn, Craig Mermel, Jill Mesirov, Stefano Monti, Huy Nguyen, Melissa Parkin, Michael Reich, Nicolas Stransky, Barbara A. Weir, Levi Garraway, Todd Golub, Matthew Meyerson, Lynda Chin, Alexei Protopopov, Jianhua Zhang, Ilana Perna, Sandy Aronson, Narayanan Sathiamoorthy, Georgia Ren, Jun Yao, W. Ruprecht Wiedemeyer, Hyunsoo Kim, Won Kong Sek, Yonghong Xiao, Isaac S. Kohane, Jon Seidman, Peter J. Park, Raju Kucherlapati, Peter W. Laird, Leslie Cope, James G. Herman, Daniel J. Weisenberger, Fei Pan, David Van Den Berg, Leander Van Neste, Mi Yi Joo, Kornel E. Schuebel, Stephen B. Baylin, Devin M. Absher, Jun Z. Li, Audrey Southwick, Shannon Brady, Amita Aggarwal, Tisha Chung, Gavin Sherlock, James D. Brooks, Richard M. Myers, Paul Spellman, Elizabeth Purdom, Lakshmi R. Jakkula, Anna V. Lapuk, Henry Marr, Shannon Dorton, Gi Choi Yoon, Ju Han, Amrita Ray, Victoria Wang, Steffen Durinck, Mark Robinson, Nicholas J. Wang, Karen Vranizan, Vivian Peng, Eric Van Name, Gerald V. Fontenay, John Ngai, John G. Conboy, Bahram Parvin, Heidi Feiler, Terence P. Speed, Joe Gray, Cameron Brennan, Nicholas D. Socci, Adam Olshen, Barry S. Taylor, Alex Lash, Nikolaus Schultz, Boris Reva, Yevgeniy Antipin, Alexey Stukalov, Benjamin Gross, Ethan Cerami, Qing Wang Wei, Li Xuan Qin, Venkatraman E. Seshan, Liliana Villafania, Magali Cavatore, Laetitia Borsu, Agnes Viale, William Gerald, Chris Sander, Marc Ladanyi, Charles M. Perou, D. Neil Hayes, Michael D. Topal, Katherine A. Hoadley, Yuan Qi, Sai Balu, Yan Shi, Junyuan Wu, Robert Penny, Michael Bittner, Troy Shelton, Elizabeth Lenkiewicz, Scott Morris, Debbie Beasley, Sheri Sanders, Ari Kahn, Robert Sfeir, Jessica Chen, David Nassau, Larry Feng, Erin Hickey, Anna Barker, Daniela S. Gerhard, Joseph Vockley, Carolyn Compton, Jim Vaught, Peter Fielding, Martin L. Ferguson, Carl Schaefer, Jinghui Zhang, Subhashree Madhavan, Kenneth H. Buetow, Francis Collins, Peter Good, Mark Guyer, Brad Ozenberger, Jane Peterson, Elizabeth Thomson

Research output: Contribution to journalArticle

4478 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)1061-1068
Number of pages8
JournalNature
Volume455
Issue number7216
DOIs
StatePublished - Oct 23 2008
Externally publishedYes

Fingerprint

Glioblastoma
Atlases
Genes
DNA Methylation
Neoplasms
Genome
Mutation
Regulator Genes
Phosphatidylinositol 3-Kinases
Epigenomics
Brain Neoplasms
Chromosome Aberrations
Methylation
Nucleotides
Observation
Phenotype
Gene Expression
DNA
Research

ASJC Scopus subject areas

  • General

Cite this

McLendon, R., Friedman, A., Bigner, D., Van Meir, E. G., Brat, D. J., Mastrogianakis, G. M., ... Thomson, E. (2008). Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature, 455(7216), 1061-1068. https://doi.org/10.1038/nature07385

Comprehensive genomic characterization defines human glioblastoma genes and core pathways. / McLendon, Roger; Friedman, Allan; Bigner, Darrell; Van Meir, Erwin G.; Brat, Daniel J.; Mastrogianakis, Gena M.; Olson, Jeffrey J.; Mikkelsen, Tom; Lehman, Norman; Aldape, Ken; Yung, W. K Alfred; Bogler, Oliver; Weinstein, John N.; VandenBerg, Scott; Berger, Mitchel; Prados, Michael; Muzny, Donna; Morgan, Margaret; Scherer, Steve; Sabo, Aniko; Nazareth, Lynn; Lewis, Lora; Hall, Otis; Zhu, Yiming; Ren, Yanru; Alvi, Omar; Yao, Jiqiang; Hawes, Alicia; Jhangiani, Shalini; Fowler, Gerald; San Lucas, Anthony; Kovar, Christie; Cree, Andrew; Dinh, Huyen; Santibanez, Jireh; Joshi, Vandita; Gonzalez-Garay, Manuel L.; Miller, Christopher A.; Milosavljevic, Aleksandar; Donehower, Larry; Wheeler, David A.; Gibbs, Richard A.; Cibulskis, Kristian; Sougnez, Carrie; Fennell, Tim; Mahan, Scott; Wilkinson, Jane; Ziaugra, Liuda; Onofrio, Robert; Bloom, Toby; Nicol, Rob; Ardlie, Kristin; Baldwin, Jennifer; Gabriel, Stacey; Lander, Eric S.; Ding, Li; Fulton, Robert S.; McLellan, Michael D.; Wallis, John; Larson, David E.; Shi, Xiaoqi; Abbott, Rachel; Fulton, Lucinda; Chen, Ken; Koboldt, Daniel C.; Wendl, Michael C.; Meyer, Rick; Tang, Yuzhu; Lin, Ling; Osborne, John R.; Dunford-Shore, Brian H.; Miner, Tracie L.; Delehaunty, Kim; Markovic, Chris; Swift, Gary; Courtney, William; Pohl, Craig; Abbott, Scott; Hawkins, Amy; Leong, Shin; Haipek, Carrie; Schmidt, Heather; Wiechert, Maddy; Vickery, Tammi; Scott, Sacha; Dooling, David J.; Chinwalla, Asif; Weinstock, George M.; Mardis, Elaine R.; Wilson, Richard K.; Getz, Gad; Winckler, Wendy; Verhaak, Roel G W; Lawrence, Michael S.; O'Kelly, Michael; Robinson, Jim; Alexe, Gabriele; Beroukhim, Rameen; Carter, Scott; Chiang, Derek; Gould, Josh; Gupta, Supriya; Korn, Josh; Mermel, Craig; Mesirov, Jill; Monti, Stefano; Nguyen, Huy; Parkin, Melissa; Reich, Michael; Stransky, Nicolas; Weir, Barbara A.; Garraway, Levi; Golub, Todd; Meyerson, Matthew; Chin, Lynda; Protopopov, Alexei; Zhang, Jianhua; Perna, Ilana; Aronson, Sandy; Sathiamoorthy, Narayanan; Ren, Georgia; Yao, Jun; Wiedemeyer, W. Ruprecht; Kim, Hyunsoo; Sek, Won Kong; Xiao, Yonghong; Kohane, Isaac S.; Seidman, Jon; Park, Peter J.; Kucherlapati, Raju; Laird, Peter W.; Cope, Leslie; Herman, James G.; Weisenberger, Daniel J.; Pan, Fei; Van Den Berg, David; Van Neste, Leander; Joo, Mi Yi; Schuebel, Kornel E.; Baylin, Stephen B.; Absher, Devin M.; Li, Jun Z.; Southwick, Audrey; Brady, Shannon; Aggarwal, Amita; Chung, Tisha; Sherlock, Gavin; Brooks, James D.; Myers, Richard M.; Spellman, Paul; Purdom, Elizabeth; Jakkula, Lakshmi R.; Lapuk, Anna V.; Marr, Henry; Dorton, Shannon; Yoon, Gi Choi; Han, Ju; Ray, Amrita; Wang, Victoria; Durinck, Steffen; Robinson, Mark; Wang, Nicholas J.; Vranizan, Karen; Peng, Vivian; Van Name, Eric; Fontenay, Gerald V.; Ngai, John; Conboy, John G.; Parvin, Bahram; Feiler, Heidi; Speed, Terence P.; Gray, Joe; Brennan, Cameron; Socci, Nicholas D.; Olshen, Adam; Taylor, Barry S.; Lash, Alex; Schultz, Nikolaus; Reva, Boris; Antipin, Yevgeniy; Stukalov, Alexey; Gross, Benjamin; Cerami, Ethan; Wei, Qing Wang; Qin, Li Xuan; Seshan, Venkatraman E.; Villafania, Liliana; Cavatore, Magali; Borsu, Laetitia; Viale, Agnes; Gerald, William; Sander, Chris; Ladanyi, Marc; Perou, Charles M.; Hayes, D. Neil; Topal, Michael D.; Hoadley, Katherine A.; Qi, Yuan; Balu, Sai; Shi, Yan; Wu, Junyuan; Penny, Robert; Bittner, Michael; Shelton, Troy; Lenkiewicz, Elizabeth; Morris, Scott; Beasley, Debbie; Sanders, Sheri; Kahn, Ari; Sfeir, Robert; Chen, Jessica; Nassau, David; Feng, Larry; Hickey, Erin; Barker, Anna; Gerhard, Daniela S.; Vockley, Joseph; Compton, Carolyn; Vaught, Jim; Fielding, Peter; Ferguson, Martin L.; Schaefer, Carl; Zhang, Jinghui; Madhavan, Subhashree; Buetow, Kenneth H.; Collins, Francis; Good, Peter; Guyer, Mark; Ozenberger, Brad; Peterson, Jane; Thomson, Elizabeth.

In: Nature, Vol. 455, No. 7216, 23.10.2008, p. 1061-1068.

Research output: Contribution to journalArticle

McLendon, R, Friedman, A, Bigner, D, Van Meir, EG, Brat, DJ, Mastrogianakis, GM, Olson, JJ, Mikkelsen, T, Lehman, N, Aldape, K, Yung, WKA, Bogler, O, Weinstein, JN, VandenBerg, S, Berger, M, Prados, M, Muzny, D, Morgan, M, Scherer, S, Sabo, A, Nazareth, L, Lewis, L, Hall, O, Zhu, Y, Ren, Y, Alvi, O, Yao, J, Hawes, A, Jhangiani, S, Fowler, G, San Lucas, A, Kovar, C, Cree, A, Dinh, H, Santibanez, J, Joshi, V, Gonzalez-Garay, ML, Miller, CA, Milosavljevic, A, Donehower, L, Wheeler, DA, Gibbs, RA, Cibulskis, K, Sougnez, C, Fennell, T, Mahan, S, Wilkinson, J, Ziaugra, L, Onofrio, R, Bloom, T, Nicol, R, Ardlie, K, Baldwin, J, Gabriel, S, Lander, ES, Ding, L, Fulton, RS, McLellan, MD, Wallis, J, Larson, DE, Shi, X, Abbott, R, Fulton, L, Chen, K, Koboldt, DC, Wendl, MC, Meyer, R, Tang, Y, Lin, L, Osborne, JR, Dunford-Shore, BH, Miner, TL, Delehaunty, K, Markovic, C, Swift, G, Courtney, W, Pohl, C, Abbott, S, Hawkins, A, Leong, S, Haipek, C, Schmidt, H, Wiechert, M, Vickery, T, Scott, S, Dooling, DJ, Chinwalla, A, Weinstock, GM, Mardis, ER, Wilson, RK, Getz, G, Winckler, W, Verhaak, RGW, Lawrence, MS, O'Kelly, M, Robinson, J, Alexe, G, Beroukhim, R, Carter, S, Chiang, D, Gould, J, Gupta, S, Korn, J, Mermel, C, Mesirov, J, Monti, S, Nguyen, H, Parkin, M, Reich, M, Stransky, N, Weir, BA, Garraway, L, Golub, T, Meyerson, M, Chin, L, Protopopov, A, Zhang, J, Perna, I, Aronson, S, Sathiamoorthy, N, Ren, G, Yao, J, Wiedemeyer, WR, Kim, H, Sek, WK, Xiao, Y, Kohane, IS, Seidman, J, Park, PJ, Kucherlapati, R, Laird, PW, Cope, L, Herman, JG, Weisenberger, DJ, Pan, F, Van Den Berg, D, Van Neste, L, Joo, MY, Schuebel, KE, Baylin, SB, Absher, DM, Li, JZ, Southwick, A, Brady, S, Aggarwal, A, Chung, T, Sherlock, G, Brooks, JD, Myers, RM, Spellman, P, Purdom, E, Jakkula, LR, Lapuk, AV, Marr, H, Dorton, S, Yoon, GC, Han, J, Ray, A, Wang, V, Durinck, S, Robinson, M, Wang, NJ, Vranizan, K, Peng, V, Van Name, E, Fontenay, GV, Ngai, J, Conboy, JG, Parvin, B, Feiler, H, Speed, TP, Gray, J, Brennan, C, Socci, ND, Olshen, A, Taylor, BS, Lash, A, Schultz, N, Reva, B, Antipin, Y, Stukalov, A, Gross, B, Cerami, E, Wei, QW, Qin, LX, Seshan, VE, Villafania, L, Cavatore, M, Borsu, L, Viale, A, Gerald, W, Sander, C, Ladanyi, M, Perou, CM, Hayes, DN, Topal, MD, Hoadley, KA, Qi, Y, Balu, S, Shi, Y, Wu, J, Penny, R, Bittner, M, Shelton, T, Lenkiewicz, E, Morris, S, Beasley, D, Sanders, S, Kahn, A, Sfeir, R, Chen, J, Nassau, D, Feng, L, Hickey, E, Barker, A, Gerhard, DS, Vockley, J, Compton, C, Vaught, J, Fielding, P, Ferguson, ML, Schaefer, C, Zhang, J, Madhavan, S, Buetow, KH, Collins, F, Good, P, Guyer, M, Ozenberger, B, Peterson, J & Thomson, E 2008, 'Comprehensive genomic characterization defines human glioblastoma genes and core pathways', Nature, vol. 455, no. 7216, pp. 1061-1068. https://doi.org/10.1038/nature07385
McLendon R, Friedman A, Bigner D, Van Meir EG, Brat DJ, Mastrogianakis GM et al. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008 Oct 23;455(7216):1061-1068. https://doi.org/10.1038/nature07385
McLendon, Roger ; Friedman, Allan ; Bigner, Darrell ; Van Meir, Erwin G. ; Brat, Daniel J. ; Mastrogianakis, Gena M. ; Olson, Jeffrey J. ; Mikkelsen, Tom ; Lehman, Norman ; Aldape, Ken ; Yung, W. K Alfred ; Bogler, Oliver ; Weinstein, John N. ; VandenBerg, Scott ; Berger, Mitchel ; Prados, Michael ; Muzny, Donna ; Morgan, Margaret ; Scherer, Steve ; Sabo, Aniko ; Nazareth, Lynn ; Lewis, Lora ; Hall, Otis ; Zhu, Yiming ; Ren, Yanru ; Alvi, Omar ; Yao, Jiqiang ; Hawes, Alicia ; Jhangiani, Shalini ; Fowler, Gerald ; San Lucas, Anthony ; Kovar, Christie ; Cree, Andrew ; Dinh, Huyen ; Santibanez, Jireh ; Joshi, Vandita ; Gonzalez-Garay, Manuel L. ; Miller, Christopher A. ; Milosavljevic, Aleksandar ; Donehower, Larry ; Wheeler, David A. ; Gibbs, Richard A. ; Cibulskis, Kristian ; Sougnez, Carrie ; Fennell, Tim ; Mahan, Scott ; Wilkinson, Jane ; Ziaugra, Liuda ; Onofrio, Robert ; Bloom, Toby ; Nicol, Rob ; Ardlie, Kristin ; Baldwin, Jennifer ; Gabriel, Stacey ; Lander, Eric S. ; Ding, Li ; Fulton, Robert S. ; McLellan, Michael D. ; Wallis, John ; Larson, David E. ; Shi, Xiaoqi ; Abbott, Rachel ; Fulton, Lucinda ; Chen, Ken ; Koboldt, Daniel C. ; Wendl, Michael C. ; Meyer, Rick ; Tang, Yuzhu ; Lin, Ling ; Osborne, John R. ; Dunford-Shore, Brian H. ; Miner, Tracie L. ; Delehaunty, Kim ; Markovic, Chris ; Swift, Gary ; Courtney, William ; Pohl, Craig ; Abbott, Scott ; Hawkins, Amy ; Leong, Shin ; Haipek, Carrie ; Schmidt, Heather ; Wiechert, Maddy ; Vickery, Tammi ; Scott, Sacha ; Dooling, David J. ; Chinwalla, Asif ; Weinstock, George M. ; Mardis, Elaine R. ; Wilson, Richard K. ; Getz, Gad ; Winckler, Wendy ; Verhaak, Roel G W ; Lawrence, Michael S. ; O'Kelly, Michael ; Robinson, Jim ; Alexe, Gabriele ; Beroukhim, Rameen ; Carter, Scott ; Chiang, Derek ; Gould, Josh ; Gupta, Supriya ; Korn, Josh ; Mermel, Craig ; Mesirov, Jill ; Monti, Stefano ; Nguyen, Huy ; Parkin, Melissa ; Reich, Michael ; Stransky, Nicolas ; Weir, Barbara A. ; Garraway, Levi ; Golub, Todd ; Meyerson, Matthew ; Chin, Lynda ; Protopopov, Alexei ; Zhang, Jianhua ; Perna, Ilana ; Aronson, Sandy ; Sathiamoorthy, Narayanan ; Ren, Georgia ; Yao, Jun ; Wiedemeyer, W. Ruprecht ; Kim, Hyunsoo ; Sek, Won Kong ; Xiao, Yonghong ; Kohane, Isaac S. ; Seidman, Jon ; Park, Peter J. ; Kucherlapati, Raju ; Laird, Peter W. ; Cope, Leslie ; Herman, James G. ; Weisenberger, Daniel J. ; Pan, Fei ; Van Den Berg, David ; Van Neste, Leander ; Joo, Mi Yi ; Schuebel, Kornel E. ; Baylin, Stephen B. ; Absher, Devin M. ; Li, Jun Z. ; Southwick, Audrey ; Brady, Shannon ; Aggarwal, Amita ; Chung, Tisha ; Sherlock, Gavin ; Brooks, James D. ; Myers, Richard M. ; Spellman, Paul ; Purdom, Elizabeth ; Jakkula, Lakshmi R. ; Lapuk, Anna V. ; Marr, Henry ; Dorton, Shannon ; Yoon, Gi Choi ; Han, Ju ; Ray, Amrita ; Wang, Victoria ; Durinck, Steffen ; Robinson, Mark ; Wang, Nicholas J. ; Vranizan, Karen ; Peng, Vivian ; Van Name, Eric ; Fontenay, Gerald V. ; Ngai, John ; Conboy, John G. ; Parvin, Bahram ; Feiler, Heidi ; Speed, Terence P. ; Gray, Joe ; Brennan, Cameron ; Socci, Nicholas D. ; Olshen, Adam ; Taylor, Barry S. ; Lash, Alex ; Schultz, Nikolaus ; Reva, Boris ; Antipin, Yevgeniy ; Stukalov, Alexey ; Gross, Benjamin ; Cerami, Ethan ; Wei, Qing Wang ; Qin, Li Xuan ; Seshan, Venkatraman E. ; Villafania, Liliana ; Cavatore, Magali ; Borsu, Laetitia ; Viale, Agnes ; Gerald, William ; Sander, Chris ; Ladanyi, Marc ; Perou, Charles M. ; Hayes, D. Neil ; Topal, Michael D. ; Hoadley, Katherine A. ; Qi, Yuan ; Balu, Sai ; Shi, Yan ; Wu, Junyuan ; Penny, Robert ; Bittner, Michael ; Shelton, Troy ; Lenkiewicz, Elizabeth ; Morris, Scott ; Beasley, Debbie ; Sanders, Sheri ; Kahn, Ari ; Sfeir, Robert ; Chen, Jessica ; Nassau, David ; Feng, Larry ; Hickey, Erin ; Barker, Anna ; Gerhard, Daniela S. ; Vockley, Joseph ; Compton, Carolyn ; Vaught, Jim ; Fielding, Peter ; Ferguson, Martin L. ; Schaefer, Carl ; Zhang, Jinghui ; Madhavan, Subhashree ; Buetow, Kenneth H. ; Collins, Francis ; Good, Peter ; Guyer, Mark ; Ozenberger, Brad ; Peterson, Jane ; Thomson, Elizabeth. / Comprehensive genomic characterization defines human glioblastoma genes and core pathways. In: Nature. 2008 ; Vol. 455, No. 7216. pp. 1061-1068.
@article{549815f9ddaf4d8dbfd63db4d425554e,
title = "Comprehensive genomic characterization defines human glioblastoma genes and core pathways",
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 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 = "Roger McLendon and Allan Friedman and Darrell Bigner and {Van Meir}, {Erwin G.} and Brat, {Daniel J.} and Mastrogianakis, {Gena M.} and Olson, {Jeffrey J.} and Tom Mikkelsen and Norman Lehman and Ken Aldape and Yung, {W. K Alfred} and Oliver Bogler and Weinstein, {John N.} and Scott VandenBerg and Mitchel Berger and Michael Prados and Donna Muzny and Margaret Morgan and Steve Scherer and Aniko Sabo and Lynn Nazareth and Lora Lewis and Otis Hall and Yiming Zhu and Yanru Ren and Omar Alvi and Jiqiang Yao and Alicia Hawes and Shalini Jhangiani and Gerald Fowler and {San Lucas}, Anthony and Christie Kovar and Andrew Cree and Huyen Dinh and Jireh Santibanez and Vandita Joshi and Gonzalez-Garay, {Manuel L.} and Miller, {Christopher A.} and Aleksandar Milosavljevic and Larry Donehower and Wheeler, {David A.} and Gibbs, {Richard A.} and Kristian Cibulskis and Carrie Sougnez and Tim Fennell and Scott Mahan and Jane Wilkinson and Liuda Ziaugra and Robert Onofrio and Toby Bloom and Rob Nicol and Kristin Ardlie and Jennifer Baldwin and Stacey Gabriel and Lander, {Eric S.} and Li Ding and Fulton, {Robert S.} and McLellan, {Michael D.} and John Wallis and Larson, {David E.} and Xiaoqi Shi and Rachel Abbott and Lucinda Fulton and Ken Chen and Koboldt, {Daniel C.} and Wendl, {Michael C.} and Rick Meyer and Yuzhu Tang and Ling Lin and Osborne, {John R.} and Dunford-Shore, {Brian H.} and Miner, {Tracie L.} and Kim Delehaunty and Chris Markovic and Gary Swift and William Courtney and Craig Pohl and Scott Abbott and Amy Hawkins and Shin Leong and Carrie Haipek and Heather Schmidt and Maddy Wiechert and Tammi Vickery and Sacha Scott and Dooling, {David J.} and Asif Chinwalla and Weinstock, {George M.} and Mardis, {Elaine R.} and Wilson, {Richard K.} and Gad Getz and Wendy Winckler and Verhaak, {Roel G W} and Lawrence, {Michael S.} and Michael O'Kelly and Jim Robinson and Gabriele Alexe and Rameen Beroukhim and Scott Carter and Derek Chiang and Josh Gould and Supriya Gupta and Josh Korn and Craig Mermel and Jill Mesirov and Stefano Monti and Huy Nguyen and Melissa Parkin and Michael Reich and Nicolas Stransky and Weir, {Barbara A.} and Levi Garraway and Todd Golub and Matthew Meyerson and Lynda Chin and Alexei Protopopov and Jianhua Zhang and Ilana Perna and Sandy Aronson and Narayanan Sathiamoorthy and Georgia Ren and Jun Yao and Wiedemeyer, {W. Ruprecht} and Hyunsoo Kim and Sek, {Won Kong} and Yonghong Xiao and Kohane, {Isaac S.} and Jon Seidman and Park, {Peter J.} and Raju Kucherlapati and Laird, {Peter W.} and Leslie Cope and Herman, {James G.} and Weisenberger, {Daniel J.} and Fei Pan and {Van Den Berg}, David and {Van Neste}, Leander and Joo, {Mi Yi} and Schuebel, {Kornel E.} and Baylin, {Stephen B.} and Absher, {Devin M.} and Li, {Jun Z.} and Audrey Southwick and Shannon Brady and Amita Aggarwal and Tisha Chung and Gavin Sherlock and Brooks, {James D.} and Myers, {Richard M.} and Paul Spellman and Elizabeth Purdom and Jakkula, {Lakshmi R.} and Lapuk, {Anna V.} and Henry Marr and Shannon Dorton and Yoon, {Gi Choi} and Ju Han and Amrita Ray and Victoria Wang and Steffen Durinck and Mark Robinson and Wang, {Nicholas J.} and Karen Vranizan and Vivian Peng and {Van Name}, Eric and Fontenay, {Gerald V.} and John Ngai and Conboy, {John G.} and Bahram Parvin and Heidi Feiler and Speed, {Terence P.} and Joe Gray and Cameron Brennan and Socci, {Nicholas D.} and Adam Olshen and Taylor, {Barry S.} and Alex Lash and Nikolaus Schultz and Boris Reva and Yevgeniy Antipin and Alexey Stukalov and Benjamin Gross and Ethan Cerami and Wei, {Qing Wang} and Qin, {Li Xuan} and Seshan, {Venkatraman E.} and Liliana Villafania and Magali Cavatore and Laetitia Borsu and Agnes Viale and William Gerald and Chris Sander and Marc Ladanyi and Perou, {Charles M.} and Hayes, {D. Neil} and Topal, {Michael D.} and Hoadley, {Katherine A.} and Yuan Qi and Sai Balu and Yan Shi and Junyuan Wu and Robert Penny and Michael Bittner and Troy Shelton and Elizabeth Lenkiewicz and Scott Morris and Debbie Beasley and Sheri Sanders and Ari Kahn and Robert Sfeir and Jessica Chen and David Nassau and Larry Feng and Erin Hickey and Anna Barker and Gerhard, {Daniela S.} and Joseph Vockley and Carolyn Compton and Jim Vaught and Peter Fielding and Ferguson, {Martin L.} and Carl Schaefer and Jinghui Zhang and Subhashree Madhavan and Buetow, {Kenneth H.} and Francis Collins and Peter Good and Mark Guyer and Brad Ozenberger and Jane Peterson and Elizabeth Thomson",
year = "2008",
month = "10",
day = "23",
doi = "10.1038/nature07385",
language = "English (US)",
volume = "455",
pages = "1061--1068",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7216",

}

TY - JOUR

T1 - Comprehensive genomic characterization defines human glioblastoma genes and core pathways

AU - McLendon, Roger

AU - Friedman, Allan

AU - Bigner, Darrell

AU - Van Meir, Erwin G.

AU - Brat, Daniel J.

AU - Mastrogianakis, Gena M.

AU - Olson, Jeffrey J.

AU - Mikkelsen, Tom

AU - Lehman, Norman

AU - Aldape, Ken

AU - Yung, W. K Alfred

AU - Bogler, Oliver

AU - Weinstein, John N.

AU - VandenBerg, Scott

AU - Berger, Mitchel

AU - Prados, Michael

AU - Muzny, Donna

AU - Morgan, Margaret

AU - Scherer, Steve

AU - Sabo, Aniko

AU - Nazareth, Lynn

AU - Lewis, Lora

AU - Hall, Otis

AU - Zhu, Yiming

AU - Ren, Yanru

AU - Alvi, Omar

AU - Yao, Jiqiang

AU - Hawes, Alicia

AU - Jhangiani, Shalini

AU - Fowler, Gerald

AU - San Lucas, Anthony

AU - Kovar, Christie

AU - Cree, Andrew

AU - Dinh, Huyen

AU - Santibanez, Jireh

AU - Joshi, Vandita

AU - Gonzalez-Garay, Manuel L.

AU - Miller, Christopher A.

AU - Milosavljevic, Aleksandar

AU - Donehower, Larry

AU - Wheeler, David A.

AU - Gibbs, Richard A.

AU - Cibulskis, Kristian

AU - Sougnez, Carrie

AU - Fennell, Tim

AU - Mahan, Scott

AU - Wilkinson, Jane

AU - Ziaugra, Liuda

AU - Onofrio, Robert

AU - Bloom, Toby

AU - Nicol, Rob

AU - Ardlie, Kristin

AU - Baldwin, Jennifer

AU - Gabriel, Stacey

AU - Lander, Eric S.

AU - Ding, Li

AU - Fulton, Robert S.

AU - McLellan, Michael D.

AU - Wallis, John

AU - Larson, David E.

AU - Shi, Xiaoqi

AU - Abbott, Rachel

AU - Fulton, Lucinda

AU - Chen, Ken

AU - Koboldt, Daniel C.

AU - Wendl, Michael C.

AU - Meyer, Rick

AU - Tang, Yuzhu

AU - Lin, Ling

AU - Osborne, John R.

AU - Dunford-Shore, Brian H.

AU - Miner, Tracie L.

AU - Delehaunty, Kim

AU - Markovic, Chris

AU - Swift, Gary

AU - Courtney, William

AU - Pohl, Craig

AU - Abbott, Scott

AU - Hawkins, Amy

AU - Leong, Shin

AU - Haipek, Carrie

AU - Schmidt, Heather

AU - Wiechert, Maddy

AU - Vickery, Tammi

AU - Scott, Sacha

AU - Dooling, David J.

AU - Chinwalla, Asif

AU - Weinstock, George M.

AU - Mardis, Elaine R.

AU - Wilson, Richard K.

AU - Getz, Gad

AU - Winckler, Wendy

AU - Verhaak, Roel G W

AU - Lawrence, Michael S.

AU - O'Kelly, Michael

AU - Robinson, Jim

AU - Alexe, Gabriele

AU - Beroukhim, Rameen

AU - Carter, Scott

AU - Chiang, Derek

AU - Gould, Josh

AU - Gupta, Supriya

AU - Korn, Josh

AU - Mermel, Craig

AU - Mesirov, Jill

AU - Monti, Stefano

AU - Nguyen, Huy

AU - Parkin, Melissa

AU - Reich, Michael

AU - Stransky, Nicolas

AU - Weir, Barbara A.

AU - Garraway, Levi

AU - Golub, Todd

AU - Meyerson, Matthew

AU - Chin, Lynda

AU - Protopopov, Alexei

AU - Zhang, Jianhua

AU - Perna, Ilana

AU - Aronson, Sandy

AU - Sathiamoorthy, Narayanan

AU - Ren, Georgia

AU - Yao, Jun

AU - Wiedemeyer, W. Ruprecht

AU - Kim, Hyunsoo

AU - Sek, Won Kong

AU - Xiao, Yonghong

AU - Kohane, Isaac S.

AU - Seidman, Jon

AU - Park, Peter J.

AU - Kucherlapati, Raju

AU - Laird, Peter W.

AU - Cope, Leslie

AU - Herman, James G.

AU - Weisenberger, Daniel J.

AU - Pan, Fei

AU - Van Den Berg, David

AU - Van Neste, Leander

AU - Joo, Mi Yi

AU - Schuebel, Kornel E.

AU - Baylin, Stephen B.

AU - Absher, Devin M.

AU - Li, Jun Z.

AU - Southwick, Audrey

AU - Brady, Shannon

AU - Aggarwal, Amita

AU - Chung, Tisha

AU - Sherlock, Gavin

AU - Brooks, James D.

AU - Myers, Richard M.

AU - Spellman, Paul

AU - Purdom, Elizabeth

AU - Jakkula, Lakshmi R.

AU - Lapuk, Anna V.

AU - Marr, Henry

AU - Dorton, Shannon

AU - Yoon, Gi Choi

AU - Han, Ju

AU - Ray, Amrita

AU - Wang, Victoria

AU - Durinck, Steffen

AU - Robinson, Mark

AU - Wang, Nicholas J.

AU - Vranizan, Karen

AU - Peng, Vivian

AU - Van Name, Eric

AU - Fontenay, Gerald V.

AU - Ngai, John

AU - Conboy, John G.

AU - Parvin, Bahram

AU - Feiler, Heidi

AU - Speed, Terence P.

AU - Gray, Joe

AU - Brennan, Cameron

AU - Socci, Nicholas D.

AU - Olshen, Adam

AU - Taylor, Barry S.

AU - Lash, Alex

AU - Schultz, Nikolaus

AU - Reva, Boris

AU - Antipin, Yevgeniy

AU - Stukalov, Alexey

AU - Gross, Benjamin

AU - Cerami, Ethan

AU - Wei, Qing Wang

AU - Qin, Li Xuan

AU - Seshan, Venkatraman E.

AU - Villafania, Liliana

AU - Cavatore, Magali

AU - Borsu, Laetitia

AU - Viale, Agnes

AU - Gerald, William

AU - Sander, Chris

AU - Ladanyi, Marc

AU - Perou, Charles M.

AU - Hayes, D. Neil

AU - Topal, Michael D.

AU - Hoadley, Katherine A.

AU - Qi, Yuan

AU - Balu, Sai

AU - Shi, Yan

AU - Wu, Junyuan

AU - Penny, Robert

AU - Bittner, Michael

AU - Shelton, Troy

AU - Lenkiewicz, Elizabeth

AU - Morris, Scott

AU - Beasley, Debbie

AU - Sanders, Sheri

AU - Kahn, Ari

AU - Sfeir, Robert

AU - Chen, Jessica

AU - Nassau, David

AU - Feng, Larry

AU - Hickey, Erin

AU - Barker, Anna

AU - Gerhard, Daniela S.

AU - Vockley, Joseph

AU - Compton, Carolyn

AU - Vaught, Jim

AU - Fielding, Peter

AU - Ferguson, Martin L.

AU - Schaefer, Carl

AU - Zhang, Jinghui

AU - Madhavan, Subhashree

AU - Buetow, Kenneth H.

AU - Collins, Francis

AU - Good, Peter

AU - Guyer, Mark

AU - Ozenberger, Brad

AU - Peterson, Jane

AU - Thomson, Elizabeth

PY - 2008/10/23

Y1 - 2008/10/23

N2 - 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 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.

AB - 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 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.

UR - http://www.scopus.com/inward/record.url?scp=54549108740&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54549108740&partnerID=8YFLogxK

U2 - 10.1038/nature07385

DO - 10.1038/nature07385

M3 - Article

C2 - 18772890

AN - SCOPUS:54549108740

VL - 455

SP - 1061

EP - 1068

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7216

ER -