MSH2, MSH6, MLH1, and PMS2 immunohistochemistry as highly sensitive screening method for DNA mismatch repair deficiency syndromes in pediatric high-grade glioma DOI Creative Commons

Lea L. Friker,

Thomas Perwein,

Andreas Waha

et al.

Acta Neuropathologica, Journal Year: 2025, Volume and Issue: 149(1)

Published: Feb. 2, 2025

Abstract 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 this study was to establish a generalized screening for Lynch syndrome constitutional MMR deficiency (CMMRD) pedHGG patients, detection deficiencies (MMRD) may enable upfront therapeutic use checkpoint inhibitors identification variant carriers patients’ families. We prospectively enrolled 155 centrally reviewed primary patients MMR-immunohistochemistry (IHC) part HIT-HGG-2013 trial protocol. MMR-IHC results were subsequently compared independently collected sequencing data (whole exome or pan-cancer panel next-generation sequencing) available HIT-HGG-2013, INFORM, MNP2.0 trials. could be successfully performed 127/155 tumor tissues. identified all present cases with CMMRD (5.5%). In addition, also detected exclusive somatic gene alterations (2.3%), including hypermethylation an alternative epigenetic silencing mechanism. Most MMRD had no family history MMRD, thus, they represented index their Cases regular protein expression never showed evidence sequencing. conclusion, presents cost-effective, relatively widely available, fast method high sensitivity (100%) specificity (96%). Given prevalence previously undetected among we strongly recommend incorporating into routine diagnostics.

Language: Английский

MSH2, MSH6, MLH1, and PMS2 immunohistochemistry as highly sensitive screening method for DNA mismatch repair deficiency syndromes in pediatric high-grade glioma DOI Creative Commons

Lea L. Friker,

Thomas Perwein,

Andreas Waha

et al.

Acta Neuropathologica, Journal Year: 2025, Volume and Issue: 149(1)

Published: Feb. 2, 2025

Abstract 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 this study was to establish a generalized screening for Lynch syndrome constitutional MMR deficiency (CMMRD) pedHGG patients, detection deficiencies (MMRD) may enable upfront therapeutic use checkpoint inhibitors identification variant carriers patients’ families. We prospectively enrolled 155 centrally reviewed primary patients MMR-immunohistochemistry (IHC) part HIT-HGG-2013 trial protocol. MMR-IHC results were subsequently compared independently collected sequencing data (whole exome or pan-cancer panel next-generation sequencing) available HIT-HGG-2013, INFORM, MNP2.0 trials. could be successfully performed 127/155 tumor tissues. identified all present cases with CMMRD (5.5%). In addition, also detected exclusive somatic gene alterations (2.3%), including hypermethylation an alternative epigenetic silencing mechanism. Most MMRD had no family history MMRD, thus, they represented index their Cases regular protein expression never showed evidence sequencing. conclusion, presents cost-effective, relatively widely available, fast method high sensitivity (100%) specificity (96%). Given prevalence previously undetected among we strongly recommend incorporating into routine diagnostics.

Language: Английский

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