Clinical and molecular heterogeneity of pineal parenchymal tumors: A consensus study Journal Article


Authors: Liu, A. P. Y.; Li, B. K.; Pfaff, E.; Gudenas, B.; Vasiljevic, A.; Orr, B. A.; Dufour, C.; Snuderl, M.; Karajannis, M. A.; Rosenblum, M. K.; Hwang, E. I.; Ng, H. K.; Hansford, J. R.; Szathmari, A.; Faure-Conter, C.; Merchant, T. E.; Levine, M.; Bouvier, N.; von Hoff, K.; Mynarek, M.; Rutkowski, S.; Sahm, F.; Kool, M.; Hawkins, C.; Onar-Thomas, A.; Robinson, G. W.; Gajjar, A.; Pfister, S. M.; Bouffet, E.; Northcott, P. A.; Jones, D. T. W.; Huang, A.
Article Title: Clinical and molecular heterogeneity of pineal parenchymal tumors: A consensus study
Abstract: 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. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.
Keywords: consensus; pineoblastoma; risk-stratification; dna methylation profiling; pineal parenchymal tumors of intermediate differentiation; molecular groups
Journal Title: Acta Neuropathologica
Volume: 141
Issue: 5
ISSN: 0001-6322
Publisher: Springer  
Date Published: 2021-05-01
Start Page: 771
End Page: 785
Language: English
DOI: 10.1007/s00401-021-02284-5
PUBMED: 33619588
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 3 May 2021 -- Source: Scopus
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MSK Authors
  1. Marc Rosenblum
    361 Rosenblum
  2. Nancy Bouvier
    45 Bouvier
  3. Max Levine
    15 Levine