Clinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study

Anthony P.Y. Liu, Bryan K. Li, Elke Pfaff, Brian Gudenas, Alexandre Vasiljevic, Brent A. Orr, Christelle Dufour, Matija Snuderl, Matthias A. Karajannis, Marc K. Rosenblum, Eugene I. Hwang, Ho Keung Ng, Jordan R. Hansford, Alexandru Szathmari, Cécile Faure-Conter, Thomas E. Merchant, Max Levine, Nancy Bouvier, Katja von Hoff, Martin MynarekStefan Rutkowski, Felix Sahm, Marcel Kool, Cynthia Hawkins, Arzu Onar-Thomas, Giles W. Robinson, Amar Gajjar, Stefan M. Pfister, Eric Bouffet, Paul A. Northcott, David T.W. Jones, Annie Huang

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

17 Citaten (Scopus)

Samenvatting

Recent genomic studies have shed light on the biology and inter-tumoral heterogeneity underlying pineal parenchymal tumors, in particular pineoblastomas (PBs) and pineal parenchymal tumors of intermediate differentiation (PPTIDs). Previous reports, however, had modest sample sizes and lacked the power to integrate molecular and clinical findings. The different proposed molecular group structures also highlighted a need to reach consensus on a robust and relevant classification system. We performed a meta-analysis on 221 patients with molecularly characterized PBs and PPTIDs. DNA methylation profiles were analyzed through complementary bioinformatic approaches and molecular subgrouping was harmonized. Demographic, clinical, and genomic features of patients and samples from these pineal tumor groups were annotated. Four clinically and biologically relevant consensus PB groups were defined: PB-miRNA1 (n = 96), PB-miRNA2 (n = 23), PB-MYC/FOXR2 (n = 34), and PB-RB1 (n = 25). A final molecularly distinct group, designated PPTID (n = 43), comprised histological PPTID and PBs. Genomic and transcriptomic profiling allowed the characterization of oncogenic drivers for individual tumor groups, specifically, alterations in the microRNA processing pathway in PB-miRNA1/2, MYC amplification and FOXR2 overexpression in PB-MYC/FOXR2, RB1 alteration in PB-RB1, and KBTBD4 insertion in PPTID. Age at diagnosis, sex predilection, and metastatic status varied significantly among tumor groups. While patients with PB-miRNA2 and PPTID had superior outcome, survival was intermediate for patients with PB-miRNA1, and dismal for those with PB-MYC/FOXR2 or PB-RB1. Reduced-dose CSI was adequate for patients with average-risk, PB-miRNA1/2 disease. We systematically interrogated the clinical and molecular heterogeneity within pineal parenchymal tumors and proposed a consensus nomenclature for disease groups, laying the groundwork for future studies as well as routine use in tumor diagnostic classification and clinical trial stratification.

Originele taal-2Engels
Pagina's (van-tot)771-785
Aantal pagina's15
TijdschriftActa Neuropathologica
Volume141
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - mei 2021

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