Papillary Tumor of the Pineal Region: A Distinct Molecular Entity

• Published in: Brain pathology (Zurich, Switzerland) Vol. 26; no. 2; pp. 199 - 205
• Main Authors: Heim, Stephanie, Sill, Martin, Jones, David T.W., Vasiljevic, Alexandre, Jouvet, Anne, Fèvre-Montange, Michelle, Wesseling, Pieter, Beschorner, Rudi, Mittelbronn, Michel, Kohlhof, Patricia, Hovestadt, Volker, Johann, Pascal, Kool, Marcel, Pajtler, Kristian W., Korshunov, Andrey, Ruland, Vincent, Sperveslage, Jan, Thomas, Christian, Witt, Hendrik, von Deimling, Andreas, Paulus, Werner, Pfister, Stefan M., Capper, David, Hasselblatt, Martin
• Format: Journal Article
• Language: English
• Published: Switzerland Blackwell Publishing Ltd 01.03.2016; John Wiley & Sons, Inc; John Wiley and Sons Inc
• Subjects: Adolescent; Adult; Brain Neoplasms - classification; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Child; Child, Preschool; Choroid Plexus Neoplasms - classification; Choroid Plexus Neoplasms - genetics; Choroid Plexus Neoplasms - metabolism; Choroid Plexus Neoplasms - pathology; Chromosome Aberrations; Chromosomes; copy number alterations; Deoxyribonucleic acid; Disease-Free Survival; DNA; DNA Methylation; DNA Mutational Analysis; ependymoma; Ependymoma - classification; Ependymoma - genetics; Ependymoma - metabolism; Ependymoma - pathology; Female; Genes; Humans; Male; Middle Aged; mRNA expression; Neoplasm Recurrence, Local; papillary tumor of the pineal region; Pineal Gland - metabolism; Pineal Gland - pathology; Pinealoma - classification; Pinealoma - genetics; Pinealoma - metabolism; Pinealoma - pathology; Polymorphism, Single Nucleotide; prognosis; RNA, Messenger - metabolism; SPDEF; Tumors; ependymoma; DNA methylation; papillary tumor of the pineal region; prognosis; copy number alterations; SPDEF; mRNA expression
• ISSN: 1015-6305; 1750-3639
• DOI: 10.1111/bpa.12282

Papillary tumor of the pineal region (PTPR) is a neuroepithelial brain tumor, which might pose diagnostic difficulties and recurs often. Little is known about underlying molecular alterations. We therefore investigated chromosomal copy number alterations, DNA methylation patterns and mRNA expression profiles in a series of 24 PTPRs. Losses of chromosome 10 were identified in all 13 PTPRs examined. Losses of chromosomes 3 and 22q (54%) as well as gains of chromosomes 8p (62%) and 12 (46%) were also common. DNA methylation profiling using Illumina 450k arrays reliably distinguished PTPR from ependymomas and pineal parenchymal tumors of intermediate differentiation. PTPR could be divided into two subgroups based on methylation pattern, PTPR group 2 showing higher global methylation and a tendency toward shorter progression‐free survival (P = 0.06). Genes overexpressed in PTPR as compared with ependymal tumors included SPDEF, known to be expressed in the rodent subcommissural organ. Notable SPDEF protein expression was encountered in 15/19 PTPRs as compared with only 2/36 ependymal tumors, 2/19 choroid plexus tumors and 0/23 samples of other central nervous system (CNS) tumor entities. In conclusion, PTPRs show typical chromosomal alterations as well as distinct DNA methylation and expression profiles, which might serve as useful diagnostic tools.