Cancer cell · 2017

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

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Mackay Alan, Burford Anna, Carvalho Diana, Izquierdo Elisa, Fazal-Salom Janat, Taylor Kathryn R, Bjerke Lynn, Clarke Matthew, Vinci Mara, Nandhabalan Meera, Temelso Sara, Popov Sergey, Molinari Valeria, Raman Pichai, Waanders Angela J, Han Harry J, Gupta Saumya, Marshall Lynley, Zacharoulis Stergios, Vaidya Sucheta, Mandeville Henry C, Bridges Leslie R, Martin Andrew J, Al-Sarraj Safa, Chandler Christopher, Ng Ho-Keung, Li Xingang, Mu Kun, Trabelsi Saoussen, Brahim Dorra H'mida-Ben, Kisljakov Alexei N, Konovalov Dmitry M, Moore Andrew S, Carcaboso Angel Montero, Sunol Mariona, de Torres Carmen, Cruz Ofelia, Mora Jaume, Shats Ludmila I, Stavale João N, Bidinotto Lucas T, Reis Rui M, Entz-Werle Natacha, Farrell Michael, Cryan Jane, Crimmins Darach, Caird John, Pears Jane, Monje Michelle, Debily Marie-Anne, Castel David, Grill Jacques, Hawkins Cynthia, Nikbakht Hamid, Jabado Nada, Baker Suzanne J, Pfister Stefan M, Jones David T W, Fouladi Maryam, von Bueren André O, Baudis Michael, Resnick Adam, Jones Chris

Аннотация

We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

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