Pediatric high-grade gliomas represent a heterogeneous group of tumors with a wide variety of molecular features. We performed whole exome sequencing and methylation profiling on matched primary and recurrent tumors from four pediatric patients with hemispheric high-grade gliomas. Genetic analysis showed the presence of some variants shared between primary and recurrent tumors, along with other variants exclusive of primary or recurrent tumors. NSD1 variants, all novel and not previously reported, were present at high frequency in our series (100%) and were all shared between the samples, independently of primary or recurrence. For every variant, in silico prediction tools estimated a high probability of altering protein function. The novel NSD1 variant (c.5924T > A; p.Leu1975His) was present in one in four cases at recurrence, and in two in four cases at primary. The novel NSD1 variant (c.5993T > A; p.Met1998Lys) was present in one in four cases both at primary and recurrence, and in one in four cases only at primary. The presence of NSD1 mutations only at recurrence may suggest that they can be sub-clonal, while the presence in both primary and recurrence implies that they can also represent early and stable events. Furthermore, their presence only in primary, but not in recurrent tumors, suggest that NSD1 mutations may also be influenced by treatment.

NSD1 mutations and pediatric high-grade gliomas: a comparative genomic study in primary and recurrent tumors / D'Amati, Antonio; Nicolussi, Arianna; Miele, Evelina; Mastronuzzi, Angela; Rossi, Sabrina; Gianno, Francesca; Buttarelli, Francesca Romana; Minasi, Simone; Lodeserto, Pietro; Paola Gardiman, Marina; Viscardi, Elisabetta; Coppa, Anna; Donofrio, Vittoria; Giovannoni, Isabella; Giangaspero, Felice; Antonelli, Manila. - In: DIAGNOSTICS. - ISSN 2075-4418. - 13:1(2022), p. 78. [10.3390/diagnostics13010078]

NSD1 mutations and pediatric high-grade gliomas: a comparative genomic study in primary and recurrent tumors

Arianna Nicolussi
Co-primo
;
Francesca Gianno;Francesca Romana Buttarelli;Simone Minasi;anna coppa;FELICE GIANGASPERO
Penultimo
;
Manila Antonelli
Ultimo
2022

Abstract

Pediatric high-grade gliomas represent a heterogeneous group of tumors with a wide variety of molecular features. We performed whole exome sequencing and methylation profiling on matched primary and recurrent tumors from four pediatric patients with hemispheric high-grade gliomas. Genetic analysis showed the presence of some variants shared between primary and recurrent tumors, along with other variants exclusive of primary or recurrent tumors. NSD1 variants, all novel and not previously reported, were present at high frequency in our series (100%) and were all shared between the samples, independently of primary or recurrence. For every variant, in silico prediction tools estimated a high probability of altering protein function. The novel NSD1 variant (c.5924T > A; p.Leu1975His) was present in one in four cases at recurrence, and in two in four cases at primary. The novel NSD1 variant (c.5993T > A; p.Met1998Lys) was present in one in four cases both at primary and recurrence, and in one in four cases only at primary. The presence of NSD1 mutations only at recurrence may suggest that they can be sub-clonal, while the presence in both primary and recurrence implies that they can also represent early and stable events. Furthermore, their presence only in primary, but not in recurrent tumors, suggest that NSD1 mutations may also be influenced by treatment.
2022
pediatric high-grade gliomas; hemispheric pediatric high-grade gliomas; high grade glioma H3-/IDH-wildtype; glioma; CNS tumors; molecular biology; WES; methylation profiling; NSD1 gene; targeted therapy
01 Pubblicazione su rivista::01a Articolo in rivista
NSD1 mutations and pediatric high-grade gliomas: a comparative genomic study in primary and recurrent tumors / D'Amati, Antonio; Nicolussi, Arianna; Miele, Evelina; Mastronuzzi, Angela; Rossi, Sabrina; Gianno, Francesca; Buttarelli, Francesca Romana; Minasi, Simone; Lodeserto, Pietro; Paola Gardiman, Marina; Viscardi, Elisabetta; Coppa, Anna; Donofrio, Vittoria; Giovannoni, Isabella; Giangaspero, Felice; Antonelli, Manila. - In: DIAGNOSTICS. - ISSN 2075-4418. - 13:1(2022), p. 78. [10.3390/diagnostics13010078]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1663589
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