Lynch syndrome-associated ultra-hypermutated pediatric glioblastoma mimicking a constitutional mismatch repair deficiency syndrome.
Adolescent
Brain Neoplasms
/ genetics
Colorectal Neoplasms
/ genetics
Colorectal Neoplasms, Hereditary Nonpolyposis
/ genetics
DNA Mismatch Repair
/ genetics
DNA-Binding Proteins
/ genetics
Glioblastoma
/ genetics
High-Throughput Nucleotide Sequencing
Humans
Male
Mutation
Neoplasm Recurrence, Local
/ genetics
Neoplastic Syndromes, Hereditary
/ genetics
neoplasm of the central nervous system
Journal
Cold Spring Harbor molecular case studies
ISSN: 2373-2873
Titre abrégé: Cold Spring Harb Mol Case Stud
Pays: United States
ID NLM: 101660017
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
07
12
2018
accepted:
19
08
2019
pubmed:
13
10
2019
medline:
21
7
2020
entrez:
13
10
2019
Statut:
epublish
Résumé
Pediatric glioblastoma multiforme (GBM) has a poor prognosis as a result of recurrence after treatment of surgery and radiochemotherapy. A small subset of pediatric GBMs presenting with an ultra-high tumor mutational burden (TMB) may be sensitive to immune checkpoint inhibition. Here we report a 16-yr-old male with an ultra-hypermutated GBM. After incomplete surgical resection, molecular analysis of the tumor identified unusually high numbers of mutations and intratumor heterogeneity by a hotspot next-generation sequencing (NGS) panel. Further comprehensive molecular profiling identified a TMB of 343 mutations/Mb. An ultra-hypermutation genotype in pediatric GBMs is suggestive of a constitutive mismatch repair deficiency syndrome (CMMRD), which often acquires additional somatic driver mutations in replicating DNA polymerase genes. Tumor sequencing identified two
Identifiants
pubmed: 31604779
pii: mcs.a003863
doi: 10.1101/mcs.a003863
pmc: PMC6824252
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2019 Yang et al.; Published by Cold Spring Harbor Laboratory Press.
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