TY  - JOUR
AU  - Friker, Lea L
AU  - Perwein, Thomas
AU  - Waha, Andreas
AU  - Dörner, Evelyn
AU  - Klein, Rebecca
AU  - Blattner-Johnson, Mirjam
AU  - Layer, Julian P
AU  - Sturm, Dominik
AU  - Nussbaumer, Gunther
AU  - Kwiecien, Robert
AU  - Spier, Isabel
AU  - Aretz, Stefan
AU  - Kerl, Kornelius
AU  - Hennewig, Ulrike
AU  - Rohde, Marius
AU  - Karow, Axel
AU  - Bluemcke, Ingmar
AU  - Schmitz, Ann Kristin
AU  - Reinhard, Harald
AU  - Hernáiz Driever, Pablo
AU  - Wendt, Susanne
AU  - Weiser, Annette
AU  - Guerreiro Stücklin, Ana S
AU  - Gerber, Nicolas U
AU  - von Bueren, André O
AU  - Khurana, Claudia
AU  - Jorch, Norbert
AU  - Wiese, Maria
AU  - Kratz, Christian P
AU  - Eyrich, Matthias
AU  - Karremann, Michael
AU  - Herrlinger, Ulrich
AU  - Hölzel, Michael
AU  - Jones, David T W
AU  - Hoffmann, Marion
AU  - Pietsch, Torsten
AU  - Gielen, Gerrit H
AU  - Kramm, Christof M
TI  - MSH2, MSH6, MLH1, and PMS2 immunohistochemistry as highly sensitive screening method for DNA mismatch repair deficiency syndromes in pediatric high-grade glioma.
JO  - Acta neuropathologica
VL  - 149
IS  - 1
SN  - 0001-6322
CY  - Heidelberg
PB  - Springer
M1  - DKFZ-2025-00278
SP  - 11
PY  - 2025
AB  - 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
KW  - Humans
KW  - Mismatch Repair Endonuclease PMS2: genetics
KW  - Mismatch Repair Endonuclease PMS2: metabolism
KW  - MutL Protein Homolog 1: genetics
KW  - MutS Homolog 2 Protein: genetics
KW  - MutS Homolog 2 Protein: metabolism
KW  - Female
KW  - Brain Neoplasms: genetics
KW  - Brain Neoplasms: pathology
KW  - Child
KW  - DNA-Binding Proteins: genetics
KW  - DNA-Binding Proteins: metabolism
KW  - Male
KW  - Glioma: genetics
KW  - Glioma: pathology
KW  - Glioma: metabolism
KW  - Immunohistochemistry: methods
KW  - Adolescent
KW  - DNA Mismatch Repair: genetics
KW  - Child, Preschool
KW  - Neoplastic Syndromes, Hereditary: genetics
KW  - Neoplastic Syndromes, Hereditary: diagnosis
KW  - Colorectal Neoplasms, Hereditary Nonpolyposis: genetics
KW  - Colorectal Neoplasms, Hereditary Nonpolyposis: pathology
KW  - Colorectal Neoplasms, Hereditary Nonpolyposis: diagnosis
KW  - Infant
KW  - Germ-Line Mutation: genetics
KW  - Colorectal Neoplasms
KW  - Constitutional mismatch repair deficiency (Other)
KW  - Immunohistochemistry (Other)
KW  - Lynch syndrome (Other)
KW  - Pediatric high-grade glioma (Other)
KW  - Mismatch Repair Endonuclease PMS2 (NLM Chemicals)
KW  - PMS2 protein, human (NLM Chemicals)
KW  - MutL Protein Homolog 1 (NLM Chemicals)
KW  - MutS Homolog 2 Protein (NLM Chemicals)
KW  - MSH2 protein, human (NLM Chemicals)
KW  - DNA-Binding Proteins (NLM Chemicals)
KW  - G-T mismatch-binding protein (NLM Chemicals)
KW  - MLH1 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39894875
DO  - DOI:10.1007/s00401-025-02846-x
UR  - https://inrepo02.dkfz.de/record/298422
ER  -