% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Mntyl:307571,
      author       = {S. Mäntylä and A. Nurminen and S. Huovinen and S.
                      Jaatinen and T. Haapaniemi and R. Nurminen and I. Hermelo
                      and S. Volz$^*$ and K. K. Maaß$^*$ and K. W. Pajtler$^*$
                      and K. Nordfors and H. Haapasalo and M. Nykter and J.
                      Haapasalo and K. J. Rautajoki},
      title        = {{G}enomic analysis of {PLNTY}-like tumor progression into
                      epithelioid glioblastoma: a case report.},
      journal      = {Acta Neuropathologica Communications},
      volume       = {nn},
      issn         = {2051-5960},
      address      = {London},
      publisher    = {Biomed Central},
      reportid     = {DKFZ-2026-00066},
      pages        = {nn},
      year         = {2026},
      note         = {#DKTKZFB26# / epub},
      abstract     = {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.},
      keywords     = {Brain tumor (Other) / Cancer (Other) / Cancer genetics
                      (Other) / Epithelioid glioblastoma (Other) /
                      Polymorphous-low-grade-neuroepithelial-of-young (Other)},
      cin          = {B062 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41508055},
      doi          = {10.1186/s40478-025-02209-3},
      url          = {https://inrepo02.dkfz.de/record/307571},
}