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

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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, Jr., Carlos Gilberto ^{[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 ^{[19, 8, 9]} ; Beroukhim, Rameen ^{[19, 8, 9, 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] ; Network, TCGA Res

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^[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] Baylor Coll Med, Houston, TX 77030 - USA

^[14] Childrens Hosp, 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

• Tipo de documento: Artigo Científico
• Fonte: Cell; v. 164, n. 3, p. 550-563, JAN 28 2016.
• Citações Web of Science: 464
• Assunto(s): Glioblastoma Neoplasias

Resumo

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. (AU)

• Processo FAPESP: 14/08321-3 - Identificação e caracterização de elementos genômicos funcionais associados com a progressão de gliomas de baixo grau a gliomas de alto grau: estudo integrado do genoma e epigenoma
• Beneficiário: Camila Ferreira de Souza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/02844-7 - Alterações epigenômicas aberrantes que são definidas por assinaturas genômicas distintas associadas a gliomas: métodos e desenvolvimento
• Beneficiário: Tiago Chedraoui Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 14/02245-3 - Identificação de assinaturas epigenômicas que definem regiões regulatórias ativas do genoma associadas à diferenciação mesenquimal a partir de células-tronco pluripotentes humanas
• Beneficiário: Tathiane Maistro Malta Pereira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/07925-5 - Softwares de código aberto contendo ferramentas estatísticas para análise e integração de conjuntos de dados epigenômicos produzidos em alta escala, a fim de decifrar e entender redes reguladoras de câncer
• Beneficiário: Houtan Noushmehr
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores