DOI: 10.1101/19012005Nov 15, 2019Paper

The efficacy of DNA MMR enzyme immunohistochemistry as a screening test for hypermutated gliomas

MedRxiv : the Preprint Server for Health Sciences
M. McCordCraig Horbinski


A subset of gliomas has DNA repair defects that lead to hypermutated genomes. While such tumors are resistant to alkylating chemotherapies, they may also express more mutant neoantigens on their cell surfaces, and thus be more responsive to immunotherapies. A fast, inexpensive method of screening for hypermutated gliomas would therefore be of great clinical value. Since immunohistochemistry (IHC) for the DNA mismatch repair (MMR) proteins Msh2, Msh6, Mlh1, and Pms2 is already used to screen for hypermutated colorectal cancers, we sought to determine whether that panel might have similar utility in gliomas. MMR IHC was scored in 100 WHO grade I-IV gliomas with known tumor mutation burdens (TMB), while blinded to TMB data. Eight of 100 cases showed loss of one or more MMR proteins by IHC, and all 8 were hypermutated. Among the remaining 94 gliomas with intact MMR IHC, only one was hypermutated; that tumor had an inactivating mutation in another DNA repair gene, ATM. Overall accuracy, sensitivity, and specificity were 99%, 89%, and 100%, respectively. The strongest correlates with hypermutation were prior TMZ treatment, MGMT promoter methylation, and IDH1 mutation. Among MMR-deficient hypermutated gliomas, 50% contained both MMR-l...Continue Reading

Related Concepts

Related Feeds

Cancer Genomics (Preprints)

Cancer genomics employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest preprints here.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Related Papers

BioRxiv : the Preprint Server for Biology
Romualdo Barroso-SousaN Wagle
International Journal of Cancer. Journal International Du Cancer
Jason K SaDo-Hyun Nam
Annals of Oncology : Official Journal of the European Society for Medical Oncology
R Barroso-SousaN Wagle
© 2021 Meta ULC. All rights reserved