Glioblastomas (GBMs) are classified into isocitrate dehydrogenase (IDH) mutants and IDH wild-types (IDH-wt). This study aimed at identifying the mutational assets of IDH-wt GBMs in patients aged 18-54 years for which limited data are available

Barresi, Valeria

Caffo, Maria

Cardali, Salvatore Massimiliano

Cingarlini, Sara

German\uf2, Antonino

Ghimenton, Claudio

Mafficini, Andrea

Piredda, Maria Liliana

Scarpa, Aldo

Simbolo, Michele

English

Background: Glioblastomas (GBMs) are classified into isocitrate dehydrogenase (IDH) mutants and IDH wild-types (IDH-wt). This study aimed at identifying the mutational assets of IDH-wt GBMs in patients aged 18&ndash;54 years for which limited data are available. Methods: Sixteen IDH-wt GBMs from adults &lt; 55 years old were explored for mutations, copy number variations, tumour mutational load (TML), and mutational spectrum by a 409 genes TML panel. Results: Eight (50%) IDH-wt GBMs were hypermutated (TML &gt; 9 mutations/Mb) and two (12.5%) were ultra-mutated (TML &gt; 100 mutations/Mb). One ultra-mutated GBM had microsatellite instability (MSI), a somatic MSH6 mutation, and a germline POLE mutation. The other ultra-mutated GBMs had MSI and two somatic mutations in MSH2. Both ultra-mutated GBMs featured at least 25% giant cells. The overall survival of eight patients with hypermutated GBMs was significantly longer than that of patients with non-hypermutated GBMs (p = 0.04). Conclusions: We identified a hyper-mutated subgroup among IDH-wt GBMs in adults &lt; 55 years that had improved prognosis. Two cases were ultra-mutated and characterized by the presence of at least 25% giant cells, MMR mutations, and MSI. Since high TML has been associated with response to immune checkpoint inhibition in paediatric gliomas, the identification of a subtype of ultra-mutated IDH-wt GBM may have implications for immunotherapy

Valeria Barresi

Michele Simbolo

Andrea Mafficini

Maria Liliana Piredda

Maria Caffo

Salvatore Massimiliano Cardali

Antonino Germanò

Sara Cingarlini

Claudio Ghimenton

Aldo Scarpa

Multidisciplinary Digital Publishing Institute

Ultra-Mutation in IDH Wild-Type Glioblastomas of Patients Younger than 55 Years is Associated with Defective Mismatch Repair, Microsatellite Instability, and Giant Cell Enrichment

Germanò, Antonino

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https://iris.univr.it/bitstream/11562/999965/2/Ultra-Mutation%20in%20IDH.pdf

Ultra-Mutation in IDH Wild-Type Glioblastomas of Patients Younger than 55 Years is Associated with Defective Mismatch Repair, Microsatellite Instability, and Giant Cell Enrichment

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Multidisciplinary Digital Publishing Institute

Catalogo dei prodotti della ricerca