TY  - JOUR
AU  - Suwala, Abigail Kora
AU  - Stichel, Damian
AU  - Schrimpf, Daniel
AU  - Kloor, Matthias
AU  - Wefers, Annika K
AU  - Reinhardt, Annekathrin
AU  - Maas, Sybren L N
AU  - Kratz, Christian P
AU  - Schweizer, Leonille
AU  - Hasselblatt, Martin
AU  - Snuderl, Matija
AU  - Abedalthagafi, Malak Sameer J
AU  - Abdullaev, Zied
AU  - Monoranu, Camelia M
AU  - Bergmann, Markus
AU  - Pekrun, Arnulf
AU  - Freyschlag, Christian
AU  - Aronica, Eleonora
AU  - Kramm, Christof M
AU  - Hinz, Felix
AU  - Sievers, Philipp
AU  - Korshunov, Andrey
AU  - Kool, Marcel
AU  - Pfister, Stefan M
AU  - Sturm, Dominik
AU  - Jones, David T W
AU  - Wick, Wolfgang
AU  - Unterberg, Andreas
AU  - Hartmann, Christian
AU  - Dodgshun, Andrew
AU  - Tabori, Uri
AU  - Wesseling, Pieter
AU  - Sahm, Felix
AU  - von Deimling, Andreas
AU  - Reuß, David
TI  - Primary mismatch repair deficient IDH-mutant astrocytoma (PMMRDIA) is a distinct type with a poor prognosis.
JO  - Acta neuropathologica
VL  - 141
IS  - 1
SN  - 1432-0533
CY  - Heidelberg
PB  - Springer
M1  - DKFZ-2020-02525
SP  - 85-100
PY  - 2021
N1  - #EA:B300#LA:B300#2021 Jan;141(1):85-100
AB  - Diffuse IDH-mutant astrocytoma mostly occurs in adults and carries a favorable prognosis compared to IDH-wildtype malignant gliomas. Acquired mismatch repair deficiency is known to occur in recurrent IDH-mutant gliomas as resistance mechanism towards alkylating chemotherapy. In this multi-institutional study, we report a novel epigenetic group of 32 IDH-mutant gliomas with proven or suspected hereditary mismatch repair deficiency. None of the tumors exhibited a combined 1p/19q deletion. These primary mismatch repair-deficient IDH-mutant astrocytomas (PMMRDIA) were histologically high-grade and were mainly found in children, adolescents and young adults (median age 14 years). Mismatch repair deficiency syndromes (Lynch or Constitutional Mismatch Repair Deficiency Syndrom (CMMRD)) were clinically diagnosed and/or germline mutations in DNA mismatch repair genes (MLH1, MSH6, MSH2) were found in all cases, except one case with a family and personal history of colon cancer and another case with MSH6-deficiency available only as recurrent tumor. Loss of at least one of the mismatch repair proteins was detected via immunohistochemistry in all, but one case analyzed. Tumors displayed a hypermutant genotype and microsatellite instability was present in more than half of the sequenced cases. Integrated somatic mutational and chromosomal copy number analyses showed frequent inactivation of TP53, RB1 and activation of RTK/PI3K/AKT pathways. In contrast to the majority of IDH-mutant gliomas, more than 60
LB  - PUB:(DE-HGF)16
C6  - pmid:33216206
DO  - DOI:10.1007/s00401-020-02243-6
UR  - https://inrepo02.dkfz.de/record/165986
ER  -