Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

被引：1577

作者：

Ceccarelli, Michele ^{[1
,2
]}

Barthel, Floris P. ^{[3
,4
]}

Malta, Tathiane M. ^{[5
,6
]}

Sabedot, Thais S. ^{[5
,6
]}

Salama, Sofie R. ^{[7
]}

Murray, Bradley A. ^{[8
,9
]}

Morozova, Olena ^{[7
]}

Newton, Yulia ^{[7
]}

Radenbaugh, Amie ^{[7
]}

Pagnotta, Stefano M. ^{[2
,10
]}

Anjum, Samreen ^{[1
]}

Wang, Jiguang ^{[11
]}

Manyam, Ganiraju ^{[3
]}

Zoppoli, Pietro ^{[11
]}

Ling, Shiyun ^{[3
]}

Rao, Arjun A. ^{[7
]}

Grifford, Mia ^{[7
]}

Cherniack, Andrew D. ^{[8
,9
]}

Zhang, Hailei ^{[8
,9
]}

Poisson, Laila ^{[12
]}

Carlotti, Carlos Gilberto, Jr. ^{[5
,6
]}

Tirapelli, Daniela Pretti da Cunha ^{[5
,6
]}

Rao, Arvind ^{[3
]}

Mikkelsen, Tom ^{[12
]}

Lau, Ching C. ^{[13
,14
]}

Yung, W. K. Alfred ^{[3
]}

Rabadan, Raul ^{[11
]}

Huse, Jason ^{[15
]}

Brat, Daniel J. ^{[16
]}

Lehman, Norman L. ^{[17
]}

Barnholtz-Sloan, Jill S. ^{[18
]}

Zheng, Siyuan ^{[3
]}

Hess, Kenneth ^{[3
]}

Rao, Ganesh ^{[3
]}

Meyerson, Matthew ^{[8
,9
,19
]}

Beroukhim, Rameen ^{[8
,9
,19
,20
]}

Cooper, Lee ^{[16
]}

Akbani, Rehan ^{[3
]}

Wrensch, Margaret ^{[21
]}

Haussler, David ^{[7
]}

Aldape, Kenneth D. ^{[22
]}

Laird, Peter W. ^{[23
]}

Gutmann, David H. ^{[24
]}

Noushmehr, Houtan ^{[5
,6
]}

Iavarone, Antonio ^{[11
]}

Verhaak, Roel G. W. ^{[3
]}

机构：

[1] Hamad Bin Khalifa Univ, Qatar Comp Res Inst, POB 5825, Doha, Qatar

[2] Univ Sannio, Dept Sci & Technol, I-82100 Benevento, Italy

[3] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Dept Bioinformat & Computat Biol,Dept Neurosurg, Dept Genom Med,Dept Biostat,Dept Neurooncol, Houston, TX 77030 USA

[4] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Oncol Grad Sch Amsterdam, NL-1081 HV Amsterdam, Netherlands

[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Dept Genet CISBi NAP, BR-14049900 Ribeirao Preto, SP, Brazil

[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Ctr Integrat Syst Biol CISBi, NAP USP, BR-14049900 Ribeirao Preto, SP, Brazil

[7] Univ Calif Santa Cruz, Genom Inst, Santa Cruz, CA 95064 USA

[8] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA

[9] Harvard Univ, Cambridge, MA 02142 USA

[10] BIOGEM Ist Ric Genetiche G Salvatore, I-83031 Campo Reale, Ariano Irpino, Italy

[11] Columbia Univ, Med Ctr, Dept Syst Biol & Biomed Informat, Dept Neurol,Dept Pathol,Inst Canc Genet, New York, NY 10032 USA

[12] Henry Ford Hosp, Detroit, MI 48202 USA

[13] Childrens Hosp, Houston, TX 77030 USA

[14] Baylor Coll Med, Houston, TX 77030 USA

[15] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA

[16] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA

[17] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA

[18] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA

[19] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[20] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA

[21] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94158 USA

[22] Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada

[23] Van Andel Res Inst, Grand Rapids, MI 49503 USA

[24] Washington Univ, Sch Med, St Louis, MO 63110 USA

来源：

CELL | 2016年 / 164卷 / 03期

基金：

巴西圣保罗研究基金会;

关键词：

TERT PROMOTER MUTATIONS; GENOMIC ANALYSIS; GRADE II; EXPRESSION; IDH1; METHYLATION; LANDSCAPE; CELLS; SURVIVAL; SUBTYPES;

D O I：

10.1016/j.cell.2015.12.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.

引用

页码：550 / 563

页数：14

共 41 条

[1] Glioblastoma Cells Containing Mutations in the Cohesin Component STAG2 Are Sensitive to PARP Inhibition [J].

Bailey, Melanie L. ;

O'Neil, Nigel J. ;

van Pel, Derek M. ;

Solomon, David A. ;

Waldman, Todd ;

Hieter, Philip .

MOLECULAR CANCER THERAPEUTICS, 2014, 13 (03) :724-732

[2] Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains [J].

Berman, Benjamin P. ;

Weisenberger, Daniel J. ;

Aman, Joseph F. ;

Hinoue, Toshinori ;

Ramjan, Zachary ;

Liu, Yaping ;

Noushmehr, Houtan ;

Lange, Christopher P. E. ;

van Dijk, Cornelis M. ;

Tollenaar, Rob A. E. M. ;

Van den Berg, David ;

Laird, Peter W. .

NATURE GENETICS, 2012, 44 (01) :40-U62

[3] TERT promoter mutations and telomerase reactivation in urothelial cancer [J].

Borah, Sumit ;

Xi, Linghe ;

Zaug, Arthur J. ;

Powell, Natasha M. ;

Dancik, Garrett M. ;

Cohen, Scott B. ;

Costello, James C. ;

Theodorescu, Dan ;

Cech, Thomas R. .

SCIENCE, 2015, 347 (6225) :1006-1010

[4] Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas [J].

Brat, Daniel J. ;

Verhaak, Roel G. W. ;

Al-dape, Kenneth D. ;

Yung, W. K. Alfred ;

Salama, Sofie R. ;

Cooper, Lee A. D. ;

Rheinbay, Esther ;

Miller, C. Ryan ;

Vitucci, Mark ;

Morozova, Olena ;

Robertson, A. Gordon ;

Noushmehr, Houtan ;

Laird, Peter W. ;

Cherniack, Andrew D. ;

Akbani, Rehan ;

Huse, Jason T. ;

Ciriello, Giovanni ;

Poisson, Laila M. ;

Barnholtz-Sloan, Jill S. ;

Berger, Mitchel S. ;

Brennan, Cameron ;

Colen, Rivka R. ;

Colman, Howard ;

Flanders, Adam E. ;

Giannini, Caterina ;

Grifford, Mia ;

Iavarone, Antonio ;

Jain, Rajan ;

Joseph, Isaac ;

Kim, Jaegil ;

Kasaian, Katayoon ;

Mikkelsen, Tom ;

Murray, Bradley A. ;

O'Neill, Brian Patrick ;

Pachter, Lior ;

Parsons, Donald W. ;

Sougnez, Carrie ;

Sulman, Erik P. ;

Vandenberg, Scott R. ;

Van Meir, Erwin G. ;

von Deimling, Andreas ;

Zhang, Hailei ;

Crain, Daniel ;

Lau, Kevin ;

Mallery, David ;

Morris, Scott ;

Paulauskis, Joseph ;

Penny, Robert ;

Shelton, Troy ;

Sherman, Mark .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (26) :2481-2498

[5] The Somatic Genomic Landscape of Glioblastoma [J].

Brennan, Cameron W. ;

Verhaak, Roel G. W. ;

McKenna, Aaron ;

Campos, Benito ;

Noushmehr, Houtan ;

Salama, Sofie R. ;

Zheng, Siyuan ;

Chakravarty, Debyani ;

Sanborn, J. Zachary ;

Berman, Samuel H. ;

Beroukhim, Rameen ;

Bernard, Brady ;

Wu, Chang-Jiun ;

Genovese, Giannicola ;

Shmulevich, Ilya ;

Barnholtz-Sloan, Jill ;

Zou, Lihua ;

Vegesna, Rahulsimham ;

Shukla, Sachet A. ;

Ciriello, Giovanni ;

Yung, W. K. ;

Zhang, Wei ;

Sougnez, Carrie ;

Mikkelsen, Tom ;

Aldape, Kenneth ;

Bigner, Darell D. ;

Van Meir, Erwin G. ;

Prados, Michael ;

Sloan, Andrew ;

Black, Keith L. ;

Eschbacher, Jennifer ;

Finocchiaro, Gaetano ;

Friedman, William ;

Andrews, David W. ;

Guha, Abhijit ;

Iacocca, Mary ;

O'Neill, Brian P. ;

Foltz, Greg ;

Myers, Jerome ;

Weisenberger, Daniel J. ;

Penny, Robert ;

Kucherlapati, Raju ;

Perou, Charles M. ;

Hayes, D. Neil ;

Gibbs, Richard ;

Marra, Marco ;

Mills, Gordon B. ;

Lander, Eric ;

Spellman, Paul ;

Wilson, Richard .

CELL, 2013, 155 (02) :462-477

[6] BRAF V600E Mutation Identifies a Subset of Low-Grade Diffusely Infiltrating Gliomas in Adults [J].

Chi, Andrew S. ;

Batchelor, Tracy T. ;

Yang, Daniel ;

Dias-Santagata, Dora ;

Borger, Darrell R. ;

Ellisen, Leif W. ;

Iafrate, A. John ;

Louis, David N. .

JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (14) :E233-E236

[7] Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors [J].

Eckel-Passow, Jeanette E. ;

Lachance, Daniel H. ;

Molinaro, Annette M. ;

Walsh, Kyle M. ;

Decker, Paul A. ;

Sicotte, Hugues ;

Pekmezci, Melike ;

Rice, Terri ;

Kosel, Matt L. ;

Smirnov, Ivan V. ;

Sarkar, Gobinda ;

Caron, Alissa A. ;

Kollmeyer, Thomas M. ;

Praska, Corinne E. ;

Chada, Anisha R. ;

Halder, Chandralekha ;

Hansen, Helen M. ;

Mccoy, Lucie S. ;

Bracci, Paige M. ;

Marshall, Roxanne ;

Zheng, Shichun ;

Reis, Gerald F. ;

Pico, Alexander R. ;

O'Neill, Brian P. ;

Buckner, Jan C. ;

Giannini, Caterina ;

Huse, Jason T. ;

Perry, Arie ;

Tihan, Tarik ;

Berger, Mitchell S. ;

Chang, Susan M. ;

Prados, Michael D. ;

Wiemels, Joseph ;

Wiencke, John K. ;

Wrensch, Margaret R. ;

Jenkins, Robert B. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (26) :2499-2508

[8] Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors [J].

Flynn, Rachel Litman ;

Cox, Kelli E. ;

Jeitany, Maya ;

Wakimoto, Hiroaki ;

Bryll, Alysia R. ;

Ganem, Neil J. ;

Bersani, Francesca ;

Pineda, Jose R. ;

Suva, Mario L. ;

Benes, Cyril H. ;

Haber, Daniel A. ;

Boussin, Francois D. ;

Zou, Lee .

SCIENCE, 2015, 347 (6219) :273-277

[9] The integrated landscape of driver genomic alterations in glioblastoma [J].

Frattini, Veronique ;

Trifonov, Vladimir ;

Chan, Joseph Minhow ;

Castano, Angelica ;

Lia, Marie ;

Abate, Francesco ;

Keir, Stephen T. ;

Ji, Alan X. ;

Zoppoli, Pietro ;

Niola, Francesco ;

Danussi, Carla ;

Dolgalev, Igor ;

Porrati, Paola ;

Pellegatta, Serena ;

Heguy, Adriana ;

Gupta, Gaurav ;

Pisapia, David J. ;

Canoll, Peter ;

Bruce, Jeffrey N. ;

McLendon, Roger E. ;

Yan, Hai ;

Aldape, Ken ;

Finocchiaro, Gaetano ;

Mikkelsen, Tom ;

Prive, Gilbert G. ;

Bigner, Darell D. ;

Lasorella, Anna ;

Rabadan, Raul ;

Iavarone, Antonio .

NATURE GENETICS, 2013, 45 (10) :1141-U270

[10] SOX2 functions to maintain neural progenitor identity [J].

Graham, V ;

Khudyakov, J ;

Ellis, P ;

Pevny, L .

NEURON, 2003, 39 (05) :749-765

← 1 2 3 4 5 →