%0 Journal Article
%A Friker, Lea L
%A Perwein, Thomas
%A Waha, Andreas
%A Dörner, Evelyn
%A Klein, Rebecca
%A Blattner-Johnson, Mirjam
%A Layer, Julian P
%A Sturm, Dominik
%A Nussbaumer, Gunther
%A Kwiecien, Robert
%A Spier, Isabel
%A Aretz, Stefan
%A Kerl, Kornelius
%A Hennewig, Ulrike
%A Rohde, Marius
%A Karow, Axel
%A Bluemcke, Ingmar
%A Schmitz, Ann Kristin
%A Reinhard, Harald
%A Hernáiz Driever, Pablo
%A Wendt, Susanne
%A Weiser, Annette
%A Guerreiro Stücklin, Ana S
%A Gerber, Nicolas U
%A von Bueren, André O
%A Khurana, Claudia
%A Jorch, Norbert
%A Wiese, Maria
%A Kratz, Christian P
%A Eyrich, Matthias
%A Karremann, Michael
%A Herrlinger, Ulrich
%A Hölzel, Michael
%A Jones, David T W
%A Hoffmann, Marion
%A Pietsch, Torsten
%A Gielen, Gerrit H
%A Kramm, Christof M
%T MSH2, MSH6, MLH1, and PMS2 immunohistochemistry as highly sensitive screening method for DNA mismatch repair deficiency syndromes in pediatric high-grade glioma.
%J Acta neuropathologica
%V 149
%N 1
%@ 0001-6322
%C Heidelberg
%I Springer
%M DKFZ-2025-00278
%P 11
%D 2025
%X Pediatric high-grade glioma (pedHGG) can occur as first manifestation of cancer predisposition syndromes resulting from pathogenic germline variants in the DNA mismatch repair (MMR) genes MSH2, MSH6, MLH1, and PMS2. The aim of this study was to establish a generalized screening for Lynch syndrome and constitutional MMR deficiency (CMMRD) in pedHGG patients, as the detection of MMR deficiencies (MMRD) may enable the upfront therapeutic use of checkpoint inhibitors and identification of variant carriers in the patients' families. We prospectively enrolled 155 centrally reviewed primary pedHGG patients for MMR-immunohistochemistry (IHC) as part of the HIT-HGG-2013 trial protocol. MMR-IHC results were subsequently compared to independently collected germline sequencing data (whole exome sequencing or pan-cancer DNA panel next-generation sequencing) available in the HIT-HGG-2013, INFORM, and MNP2.0 trials. MMR-IHC could be successfully performed in 127/155 tumor tissues. The screening identified all present cases with Lynch syndrome or CMMRD (5.5
%K Humans
%K Mismatch Repair Endonuclease PMS2: genetics
%K Mismatch Repair Endonuclease PMS2: metabolism
%K MutL Protein Homolog 1: genetics
%K MutS Homolog 2 Protein: genetics
%K MutS Homolog 2 Protein: metabolism
%K Female
%K Brain Neoplasms: genetics
%K Brain Neoplasms: pathology
%K Child
%K DNA-Binding Proteins: genetics
%K DNA-Binding Proteins: metabolism
%K Male
%K Glioma: genetics
%K Glioma: pathology
%K Glioma: metabolism
%K Immunohistochemistry: methods
%K Adolescent
%K DNA Mismatch Repair: genetics
%K Child, Preschool
%K Neoplastic Syndromes, Hereditary: genetics
%K Neoplastic Syndromes, Hereditary: diagnosis
%K Colorectal Neoplasms, Hereditary Nonpolyposis: genetics
%K Colorectal Neoplasms, Hereditary Nonpolyposis: pathology
%K Colorectal Neoplasms, Hereditary Nonpolyposis: diagnosis
%K Infant
%K Germ-Line Mutation: genetics
%K Colorectal Neoplasms
%K Constitutional mismatch repair deficiency (Other)
%K Immunohistochemistry (Other)
%K Lynch syndrome (Other)
%K Pediatric high-grade glioma (Other)
%K Mismatch Repair Endonuclease PMS2 (NLM Chemicals)
%K PMS2 protein, human (NLM Chemicals)
%K MutL Protein Homolog 1 (NLM Chemicals)
%K MutS Homolog 2 Protein (NLM Chemicals)
%K MSH2 protein, human (NLM Chemicals)
%K DNA-Binding Proteins (NLM Chemicals)
%K G-T mismatch-binding protein (NLM Chemicals)
%K MLH1 protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39894875
%R 10.1007/s00401-025-02846-x
%U https://inrepo02.dkfz.de/record/298422