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. 2016 Mar;26(2):199-205.
doi: 10.1111/bpa.12282. Epub 2015 Jul 30.

Papillary Tumor of the Pineal Region: A Distinct Molecular Entity

Stephanie Heim  1 , Martin Sill  2 , David T W Jones  3 , Alexandre Vasiljevic  4   5 , Anne Jouvet  4   5 , Michelle Fèvre-Montange  5 , Pieter Wesseling  6   7 , Rudi Beschorner  8 , Michel Mittelbronn  9 , Patricia Kohlhof  10 , Volker Hovestadt  11 , Pascal Johann  3   12 , Marcel Kool  3   12 , Kristian W Pajtler  3 , Andrey Korshunov  13   14   15 , Vincent Ruland  1 , Jan Sperveslage  16 , Christian Thomas  1 , Hendrik Witt  3   12 , Andreas von Deimling  13   14   15 , Werner Paulus  1 , Stefan M Pfister  3   14   12 , David Capper  13   14   15 , Martin Hasselblatt  1
Affiliations

Papillary Tumor of the Pineal Region: A Distinct Molecular Entity

Stephanie Heim et al. Brain Pathol. 2016 Mar.

Abstract

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.

Keywords: DNA methylation; SPDEF; copy number alterations; ependymoma; mRNA expression; papillary tumor of the pineal region; prognosis.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Genetic alterations in papillary tumors of the pineal region (PTPR): virtual karyogram showing the frequency of copy number losses (red bars) as well as gains (blue bars) as determined by molecular inversion probe single‐nucleotide polymorphism microarray. Bar width correlates with the frequency of the corresponding event (n = 13).
Figure 2
Figure 2
Methylation profiling of papillary tumors of the pineal region (PTPR): heatmap of K‐means consensus clustering of methylation profiles of PTPR, supratentorial ependymomas carrying c11orf95–RELA translocations (RELPOS), posterior fossa group A (EPN_PFA) and group B (EPN_PFB) ependymomas as well as pineal parenchymal tumors of intermediate differentiation (PPTID). Note that PTPR can be divided in two subgroups (ie, PTPR group 1 and PTPR group 2).
Figure 3
Figure 3
Expression of SPDEF in papillary tumors of the pineal region (PTPR): histopathology of PTPR (A) showing an epithelial‐like, loose papillary growth pattern (A). Note broad processes extending toward blood vessels at higher magnification (inset). Overexpression of SPDEF mRNA in PTPR (n = 4) as compared with ependymal tumors (n = 263; B). On immunohistochemistry, distinct cytoplasmic and membranous expression of SPDEF protein was present in the majority of PTPR (C: representative image of a SPDEF‐positive PTPR), but rarely observed in ependymomas, choroid plexus tumors or other brain tumors (D: representative image of an SPDEF‐negative ependymoma located in the vicinity of the third ventricle).
See this image and copyright information in PMC

References

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