Mismatch repair protein mutations in isocitrate dehydrogenase (IDH)-mutant astrocytoma and IDH-wild-type glioblastoma.
Neurooncol Adv
; 5(1): vdad085, 2023.
Article
em En
| MEDLINE
| ID: mdl-37554222
ABSTRACT
Background:
Mutations in mismatch repair (MMR) genes (MSH2, MSH6, MLH1, and PMS2) are associated with microsatellite instability and a hypermutator phenotype in numerous systemic cancers, and germline MMR mutations have been implicated in multi-organ tumor syndromes. In gliomas, MMR mutations can function as an adaptive response to alkylating chemotherapy, although there are well-documented cases of germline and sporadic mutations, with detrimental effects on patient survival.Methods:
The clinical, pathologic, and molecular features of 18 IDH-mutant astrocytomas and 20 IDH-wild-type glioblastomas with MMR mutations in the primary tumor were analyzed in comparison to 361 IDH-mutant and 906 IDH-wild-type tumors without MMR mutations. In addition, 12 IDH-mutant astrocytomas and 18 IDH-wild-type glioblastomas that developed MMR mutations between initial presentation and tumor recurrence were analyzed in comparison to 50 IDH-mutant and 104 IDH-wild-type cases that remained MMR-wild-type at recurrence.Results:
In both IDH-mutant astrocytoma and IDH-wild-type glioblastoma cohorts, the presence of MMR mutation in primary tumors was associated with significantly higher tumor mutation burden (TMB) (Pâ <â .0001); however, MMR mutations only resulted in worse overall survival in the IDH-mutant astrocytomas (Pâ =â .0069). In addition, gain of MMR mutation between the primary and recurrent surgical specimen occurred more frequently with temozolomide therapy (Pâ =â .0073), and resulted in a substantial increase in TMB (Pâ <â .0001), higher grade (Pâ =â .0119), and worse post-recurrence survival (Pâ =â .0022) in the IDH-mutant astrocytoma cohort.Conclusions:
These results suggest that whether present initially or in response to therapy, MMR mutations significantly affect TMB but appear to only influence the clinical outcome in IDH-mutant astrocytoma subsets.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Neurooncol Adv
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos