Intertumoral Heterogeneity within Medulloblastoma Subgroups

被引：877

作者：

Cavalli, Florence M. G. ^{[1
,2
]}

Remke, Marc ^{[3
,4
,79
,80
]}

Rampasek, Ladislav ^{[5
,6
]}

Peacock, John ^{[1
,2
,4
]}

Shih, David J. H. ^{[1
,2
,4
]}

Luu, Betty ^{[1
,2
]}

Garzia, Livia ^{[1
,2
]}

Torchia, Jonathon ^{[1
,4
]}

Nor, Carolina ^{[1
,2
]}

Morrissy, A. Sorana ^{[1
,2
]}

Agnihotri, Sameer ^{[7
]}

Thompson, Yuan Yao ^{[1
,2
,4
]}

Kuzan-Fischer, Claudia M. ^{[1
,2
]}

Farooq, Hamza ^{[1
,2
,4
]}

Isaev, Keren ^{[8
,9
]}

Daniels, Craig ^{[1
,2
]}

Cho, Byung-Kyu ^{[10
]}

Kim, Seung-Ki ^{[10
]}

Wang, Kyu-Chang ^{[10
]}

Lee, Ji Yeoun ^{[10
]}

Grajkowska, Wieslawa A. ^{[11
]}

Perek-Polnik, Marta ^{[12
]}

Vasiljevic, Alexandre ^{[13
,81
]}

Faure-Conter, Cecile ^{[14
]}

Jouvet, Anne ^{[15
]}

Giannini, Caterina ^{[16
]}

Rao, Amulya A. Nageswara ^{[17
]}

Li, Kay Ka Wai ^{[18
]}

Ng, Ho-Keung ^{[18
]}

Eberhart, Charles G. ^{[19
,20
,21
]}

Pollack, Ian F. ^{[22
]}

Hamilton, Ronald L. ^{[23
]}

Gillespie, G. Yancey ^{[24
]}

Olson, James M. ^{[25
,26
]}

Leary, Sarah ^{[26
]}

Weiss, William A. ^{[27
,28
,29
]}

Lach, Boleslaw ^{[30
,82
,83
]}

Chambless, Lola B. ^{[31
]}

Thompson, Reid C. ^{[31
]}

Cooper, Michael K. ^{[32
]}

Vibhakar, Rajeev ^{[33
]}

Hauser, Peter ^{[34
]}

van Veelen, Marie-Lise C. ^{[35
]}

Kros, Johan M. ^{[36
]}

French, Pim J. ^{[37
]}

Ra, Young Shin ^{[38
]}

Kumabe, Toshihiro ^{[39
]}

Lopez-Aguilar, Enrique ^{[40
]}

Zitterbart, Karel ^{[41
]}

Sterba, Jaroslav ^{[41
]}

机构：

[1] Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada

[2] Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON M5G 1X8, Canada

[3] Univ Hosp Dusseldorf, Med Fac, Dept Pediat Oncol Hematol & Clin Immunol, D-40225 Dusseldorf, Germany

[4] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON M5S 1A1, Canada

[5] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 2E4, Canada

[6] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada

[7] Univ Pittsburgh, UPCI Brain Tumor Program, Childrens Hosp Pittsburgh, Pittsburgh, PA 15224 USA

[8] Ontario Inst Canc Res, Informat Program, Toronto, ON M5G 0A3, Canada

[9] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada

[10] Seoul Natl Univ, Childrens Hosp, Div Pediat Neurosurg, Dept Neurosurg, Seoul 30322, South Korea

[11] Dept Pathol, Washington, DC USA

[12] Univ Warsaw, Childrens Mem Hlth Inst, Dept Oncol, PL-04730 Warsaw, Poland

[13] Hosp Civils Lyon, Grp Hosp Est, Ctr Biol & Pathol Est, Ctr Pathol & Neuropathol Est, F-69677 Bron, France

[14] Inst Pediat Hematol & Oncol, F-69008 Lyon, France

[15] Univ Lyon, Grp Hosp EST, Ctr Pathol EST, F-69677 Bron, France

[16] Dept Lab Med & Pathol, Minneapolis, MN USA

[17] Mayo Clin, Div Pediat Hematol Oncol, Rochester, MN 55905 USA

[18] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Shatin, Hong Kong, Peoples R China

[19] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA

[20] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA

[21] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA

[22] Univ Pittsburgh, Sch Med, Dept Neurol Surg, Pittsburgh, PA 15213 USA

[23] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA

[24] Univ Alabama Birmingham, Div Neurosurg, Dept Surg, Birmingham, AL 35233 USA

[25] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98109 USA

[26] Univ Washington, Sch Med, Div Pediat Hematol Oncol, Seattle Childrens Hosp, Seattle, WA 98145 USA

[27] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

[28] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA

[29] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA

[30] McMaster Univ, Dept Pathol & Mol Med, Div Anat Pathol, Hamilton, ON L8S 4K1, Canada

[31] Dept Neurol Surg, Madison, WI USA

[32] Vanderbilt Univ Sch Med, Dept Neurol, Nashville, TN 37232 USA

[33] Univ Colorado Denver, Dept Pediat, Aurora, CO 80045 USA

[34] Semmelweis Univ, Dept Pediat 2, H-1094 Budapest, Hungary

[35] Erasmus Univ, Med Ctr, Dept Neurosurg, NL-3000 CE Rotterdam, Netherlands

[36] Erasmus Univ, Med Ctr, Dept Pathol, NL-3000 CN Rotterdam, Netherlands

[37] Erasmus Univ, Med Ctr, Dept Neurol, NL-3015 CE Rotterdam, Netherlands

[38] Univ Ulsan, Asan Med Ctr, Dept Neurosurg, Seoul 05505, South Korea

[39] Kitasato Univ, Sch Med, Dept Neurosurg, Sagamihara, Kanagawa 2520374, Japan

[40] Hosp Pediatri Ctr Med Nacl Century XXI, Div Pediat Hematol Oncol, Mexico City 06720, DF, Mexico

[41] Masaryk Univ, Sch Med, Dept Pediat Oncol, Brno 62500, Czech Republic

[42] Ist Neurol Besta, Dept Neurooncol, Milan, Italy

[43] Fdn IRCCS Ist Nazl Tumori, I-20133 Milan, Italy

[44] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA

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

[46] Osaka Natl Hosp, Inst Clin Res, Div Stem Cell Res, Osaka 5400006, Japan

[47] Univ Debrecen, Med & Hlth Sci Ctr, Dept Neurosurg, H-4032 Debrecen, Hungary

[48] Univ Naples Federico II, Dipartimento Biochim & Biotecnol Med, I-80145 Naples, Italy

[49] Washington Univ, Sch Med, Dept Neurosurg, Div Pediat Neurosurg, St Louis, MO 63110 USA

[50] St Louis Childrens Hosp, St Louis, MO 63110 USA

来源：

CANCER CELL | 2017年 / 31卷 / 06期

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

ADULT MEDULLOBLASTOMA; MOLECULAR SUBGROUPS; GENECHIP DATA; R PACKAGE; CLASSIFICATION; MUTATIONS; SELECTION;

D O I：

10.1016/j.ccell.2017.05.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

引用

页码：737 / +

页数：24

共 45 条

[1]

Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays [J].

Aryee, Martin J. ;

Jaffe, Andrew E. ;

Corrada-Bravo, Hector ;

Ladd-Acosta, Christine ;

Feinberg, Andrew P. ;

Hansen, Kasper D. ;

Irizarry, Rafael A. .

BIOINFORMATICS, 2014, 30 (10) :1363-1369

[2]

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

[3]

Cancer Genome Atlas Research Network, 2018, Nature, V559, pE12, DOI [10.1038/nature13385, 10.1038/s41586-018-0228-6]

[4]

Integrative Genomic Analysis of Medulloblastoma Identifies a Molecular Subgroup That Drives Poor Clinical Outcome [J].

Cho, Yoon-Jae ;

Tsherniak, Aviad ;

Tamayo, Pablo ;

Santagata, Sandro ;

Ligon, Azra ;

Greulich, Heidi ;

Berhoukim, Rameen ;

Amani, Vladimir ;

Goumnerova, Liliana ;

Eberhart, Charles G. ;

Lau, Ching C. ;

Olson, James M. ;

Gilbertson, Richard J. ;

Gajjar, Amar ;

Delattre, Olivier ;

Kool, Marcel ;

Ligon, Keith ;

Meyerson, Matthew ;

Mesirov, Jill P. ;

Pomeroy, Scott L. .

JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (11) :1424-1430

[5]

Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data [J].

Dai, MH ;

Wang, PL ;

Boyd, AD ;

Kostov, G ;

Athey, B ;

Jones, EG ;

Bunney, WE ;

Myers, RM ;

Speed, TP ;

Akil, H ;

Watson, SJ ;

Meng, F .

NUCLEIC ACIDS RESEARCH, 2005, 33 (20) :e175.1-e175.9

[6]

A flexible R package for nonnegative matrix factorization [J].

Gaujoux, Renaud ;

Seoighe, Cathal .

BMC BIOINFORMATICS, 2010, 11

[7]

affy -: analysis of Affymetrix GeneChip data at the probe level [J].

Gautier, L ;

Cope, L ;

Bolstad, BM ;

Irizarry, RA .

BIOINFORMATICS, 2004, 20 (03) :307-315

[8]

MethylMix: an R package for identifying DNA methylation-driven genes [J].

Gevaert, Olivier .

BIOINFORMATICS, 2015, 31 (11) :1839-1841

[9]

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin [J].

Hoadley, Katherine A. ;

Yau, Christina ;

Wolf, Denise M. ;

Cherniack, Andrew D. ;

Tamborero, David ;

Ng, Sam ;

Leiserson, Max D. M. ;

Niu, Beifang ;

McLellan, Michael D. ;

Uzunangelov, Vladislav ;

Zhang, Jiashan ;

Kandoth, Cyriac ;

Akbani, Rehan ;

Shen, Hui ;

Omberg, Larsson ;

Chu, Andy ;

Margolin, Adam A. ;

van't Veer, Laura J. ;

Lopez-Bigas, Nuria ;

Laird, Peter W. ;

Raphael, Benjamin J. ;

Ding, Li ;

Robertson, A. Gordon ;

Byers, Lauren A. ;

Mills, Gordon B. ;

Weinstein, John N. ;

Van Waes, Carter ;

Chen, Zhong ;

Collisson, Eric A. ;

Benz, Christopher C. ;

Perou, Charles M. ;

Stuart, Joshua M. ;

Abbott, Rachel ;

Abbott, Scott ;

Aksoy, B. Arman ;

Aldape, Kenneth ;

Ally, Adrian ;

Amin, Samirkumar ;

Anastassiou, Dimitris ;

Auman, J. Todd ;

Baggerly, Keith A. ;

Balasundaram, Miruna ;

Balu, Saianand ;

Baylin, Stephen B. ;

Benz, Stephen C. ;

Berman, Benjamin P. ;

Bernard, Brady ;

Bhatt, Ami S. ;

Birol, Inanc ;

Black, Aaron D. .

CELL, 2014, 158 (04) :929-944

[10]

Robust molecular subgrouping and copy-number profiling of medulloblastoma from small amounts of archival tumour material using high-density DNA methylation arrays [J].

Hovestadt, Volker ;

Remke, Marc ;

Kool, Marcel ;

Pietsch, Torsten ;

Northcott, Paul A. ;

Fischer, Roger ;

Cavalli, Florence M. G. ;

Ramaswamy, Vijay ;

Zapatka, Marc ;

Reifenberger, Guido ;

Rutkowski, Stefan ;

Schick, Matthias ;

Bewerunge-Hudler, Melanie ;

Korshunov, Andrey ;

Lichter, Peter ;

Taylor, Michael D. ;

Pfister, Stefan M. ;

Jones, David T. W. .

ACTA NEUROPATHOLOGICA, 2013, 125 (06) :913-916

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