TY  - JOUR
AU  - Mäntylä, Sonja
AU  - Nurminen, Anssi
AU  - Huovinen, Sanna
AU  - Jaatinen, Serafiina
AU  - Haapaniemi, Teppo
AU  - Nurminen, Riikka
AU  - Hermelo, Ismaïl
AU  - Volz, Stefanie
AU  - Maaß, Kendra K
AU  - Pajtler, Kristian W
AU  - Nordfors, Kristiina
AU  - Haapasalo, Hannu
AU  - Nykter, Matti
AU  - Haapasalo, Joonas
AU  - Rautajoki, Kirsi J
TI  - Genomic analysis of PLNTY-like tumor progression into epithelioid glioblastoma: a case report.
JO  - Acta Neuropathologica Communications
VL  - nn
SN  - 2051-5960
CY  - London
PB  - Biomed Central
M1  - DKFZ-2026-00066
SP  - nn
PY  - 2026
N1  - #DKTKZFB26# / epub
AB  - Polymorphous low-grade neuroepithelial tumors of the young (PLNTY) are slow- or non-progressing epileptogenic tumors, typically occurring in young adults. These tumors are highly calcified and exhibit both diffuse growth and oligodendroglioma-like patterns. Epithelioid glioblastomas (E-GB) are rare and aggressive variants of isocitrate dehydrogenase wildtype glioblastomas (GB), associated with poor overall survival. Both PLNTY and E-GB often carry oncogenic BRAF V600E mutation (BRAFV600E). In this case study, we analyzed clinical and genetic data from a single patient who, based on extensive histological and molecular evaluation, was diagnosed to carry PLNTY-like tumor that progressed into E-GB years later. The aim of our study was to uncover the genetic drivers and the evolutionary history of these tumors. Progression of the PLNTY-like tumor into E-GB was investigated using histology, chromosomal karyotyping, whole-genome sequencing (WGS), and RNA sequencing. A typical immunohistochemical stain pattern of CD34 positivity was detected in the apparent PLNTY, whereas it was depleted in the E-GB sample, as expected. WGS analysis of the PLNTY and three E-GB samples revealed four genes with shared somatic protein-altering mutations: BRAF (carrying BRAFV600E), clonal in both PLNTY and E-GB, as well as GNS, FOXRED2, and SSTR5, which were subclonal in PLNTY and clonal in E-GB. Both the PLNTY-like and E-GB tumors also carried highly similar copy number alteration profiles with a prominent loss of heterozygosity (LOH) in the majority of the chromosomes, suggesting their monoclonal origin. PLNTY-like tumor was mainly diploid, and the tumor underwent a genome-wide duplication event during the progression to E-GB. Furthermore, two focal rearrangements leading to homozygous deletion of CDKN2A/B were detected in E-GB samples. In conclusion, this study revealed unusually extensive LOH in the histologically and genetically supported PLNTY-like tumor that progressed into E-GB. Notably, only a limited set of genetic alterations was associated with malignant transformation beyond genome duplication, the CDKN2A/B inactivation representing the best-known oncogenic driver for malignant transformation. These findings suggest that genomic profiling may be a valuable tool for the diagnosis and prognostic assessment of low-grade neuroepithelial lesions.
KW  - Brain tumor (Other)
KW  - Cancer (Other)
KW  - Cancer genetics (Other)
KW  - Epithelioid glioblastoma (Other)
KW  - Polymorphous-low-grade-neuroepithelial-of-young (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41508055
DO  - DOI:10.1186/s40478-025-02209-3
UR  - https://inrepo02.dkfz.de/record/307571
ER  -