TY - JOUR
T1 - The genetic landscape of choroid plexus tumors in children and adults
AU - Thomas, Christian
AU - Soschinski, Patrick
AU - Zwaig, Melissa
AU - Oikonomopoulos, Spyridon
AU - Okonechnikov, Konstantin
AU - Pajtler, Kristian W.
AU - Sill, Martin
AU - Schweizer, Leonille
AU - Koch, Arend
AU - Neumann, Julia
AU - Schüller, Ulrich
AU - Sahm, Felix
AU - Rauschenbach, Laurèl
AU - Keyvani, Kathy
AU - Proescholdt, Martin
AU - Riemenschneider, Markus J.
AU - Segewiß, Jochen
AU - Ruckert, Christian
AU - Grauer, Oliver
AU - Monoranu, Camelia Maria
AU - Lamszus, Katrin
AU - Patrizi, Annarita
AU - Kordes, Uwe
AU - Siebert, Reiner
AU - Kool, Marcel
AU - Ragoussis, Jiannis
AU - Paulus, Werner
AU - Rivera, Barbara
AU - Hasselblatt, Martin
N1 - Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - Background: Choroid plexus tumors (CPTs) are intraventricular brain tumors predominantly arising in children but also affecting adults. In most cases, driver mutations have not been identified, although there are reports of frequent chromosome-wide copy-number alterations and TP53 mutations, especially in choroid plexus carcinomas (CPCs). Methods: DNA methylation profiling and RNA-sequencing was performed in a series of 47 CPTs. Samples comprised 35 choroid plexus papillomas (CPPs), 6 atypical choroid plexus papillomas (aCPPs) and 6 CPCs plus three recurrences thereof. Targeted TP53 and TERT promotor sequencing was performed in all samples. Whole exome sequencing (WES) and linked-read whole genome sequencing (WGS) was performed in 25 and 4 samples, respectively. Results: Tumors comprised the molecular subgroups "pediatric A"(N=11), "pediatric B"(N=12) and "adult"(N=27). Copy-number alterations mainly represented whole-chromosomal alterations with subgroup-specific enrichments (gains of Chr1, 2 and 21q in "pediatric B"and gains of Chr5 and 9 and loss of Chr21q in "adult"). RNA sequencing yielded a novel CCDC47-PRKCA fusion transcript in one adult choroid plexus papilloma patient with aggressive clinical course; an underlying Chr17 inversion was demonstrated by linked-read WGS. WES and targeted sequencing showed TP53 mutations in 7/47 CPTs (15%), five of which were children. On the contrary, TERT promoter mutations were encountered in 7/28 adult patients (25%) and associated with shorter progression-free survival (log-rank test, p=0.015). Conclusion: Pediatric CPTs lack recurrent driver alterations except for TP53, whereas CPTs in adults show TERT promoter mutations or a novel CCDC47-PRKCA gene fusion, being associated with a more unfavorable clinical course.
AB - Background: Choroid plexus tumors (CPTs) are intraventricular brain tumors predominantly arising in children but also affecting adults. In most cases, driver mutations have not been identified, although there are reports of frequent chromosome-wide copy-number alterations and TP53 mutations, especially in choroid plexus carcinomas (CPCs). Methods: DNA methylation profiling and RNA-sequencing was performed in a series of 47 CPTs. Samples comprised 35 choroid plexus papillomas (CPPs), 6 atypical choroid plexus papillomas (aCPPs) and 6 CPCs plus three recurrences thereof. Targeted TP53 and TERT promotor sequencing was performed in all samples. Whole exome sequencing (WES) and linked-read whole genome sequencing (WGS) was performed in 25 and 4 samples, respectively. Results: Tumors comprised the molecular subgroups "pediatric A"(N=11), "pediatric B"(N=12) and "adult"(N=27). Copy-number alterations mainly represented whole-chromosomal alterations with subgroup-specific enrichments (gains of Chr1, 2 and 21q in "pediatric B"and gains of Chr5 and 9 and loss of Chr21q in "adult"). RNA sequencing yielded a novel CCDC47-PRKCA fusion transcript in one adult choroid plexus papilloma patient with aggressive clinical course; an underlying Chr17 inversion was demonstrated by linked-read WGS. WES and targeted sequencing showed TP53 mutations in 7/47 CPTs (15%), five of which were children. On the contrary, TERT promoter mutations were encountered in 7/28 adult patients (25%) and associated with shorter progression-free survival (log-rank test, p=0.015). Conclusion: Pediatric CPTs lack recurrent driver alterations except for TP53, whereas CPTs in adults show TERT promoter mutations or a novel CCDC47-PRKCA gene fusion, being associated with a more unfavorable clinical course.
KW - choroid plexus tumor
KW - fusion
KW - sequencing
KW - TERT
KW - TP53
UR - http://www.scopus.com/inward/record.url?scp=85104275417&partnerID=8YFLogxK
U2 - 10.1093/neuonc/noaa267
DO - 10.1093/neuonc/noaa267
M3 - Article
C2 - 33249490
AN - SCOPUS:85104275417
SN - 1522-8517
VL - 23
SP - 650
EP - 660
JO - Neuro-Oncology
JF - Neuro-Oncology
IS - 4
ER -