RT Journal Article
T1 Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study.
A1 Li, Bryan K
A1 Vasiljevic, Alexandre
A1 Dufour, Christelle
A1 Yao, Fupan
A1 Ho, Ben L B
A1 Lu, Mei
A1 Hwang, Eugene I
A1 Gururangan, Sridharan
A1 Hansford, Jordan R
A1 Fouladi, Maryam
A1 Nobusawa, Sumihito
A1 Laquerriere, Annie
A1 Delisle, Marie-Bernadette
A1 Fangusaro, Jason
A1 Forest, Fabien
A1 Toledano, Helen
A1 Solano-Paez, Palma
A1 Leary, Sarah
A1 Birks, Diane
A1 Hoffman, Lindsey M
A1 Szathmari, Alexandru
A1 Faure-Conter, Cécile
A1 Fan, Xing
A1 Catchpoole, Daniel
A1 Zhou, Li
A1 Schultz, Kris Ann P
A1 Ichimura, Koichi
A1 Gauchotte, Guillaume
A1 Jabado, Nada
A1 Jones, Chris
A1 Loussouarn, Delphine
A1 Mokhtari, Karima
A1 Rousseau, Audrey
A1 Ziegler, David S
A1 Tanaka, Shinya
A1 Pomeroy, Scott L
A1 Gajjar, Amar
A1 Ramaswamy, Vijay
A1 Hawkins, Cynthia
A1 Grundy, Richard G
A1 Hill, D Ashley
A1 Bouffet, Eric
A1 Huang, Annie
A1 Jouvet, Anne
K1 MYC
K1 PNET
K1 PPTID
K1 Pineoblastoma
K1 RB
K1 miRNA
AB Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1-3 arose in older children (median ages 5.2-14.0 years) and had intermediate to excellent survival (5-year OS of 68.0-100%), while Group RB and MYC PB patients were much younger (median age 1.3-1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age 
YR 2019
FD 2019-12-09
LK http://hdl.handle.net/10668/14804
UL http://hdl.handle.net/10668/14804
LA en
DS RISalud
RD Apr 20, 2025