In sporadic schwannomas, inactivation of both copies of the NF2 tumor suppressor gene on 22q is common. Constitutional mutations of SMARCB1 are responsible of schwannomatosis, an inherited tumor predisposition syndrome, characterized by the development of multiple schwannomas. We analysed the frequency of copy number changes on chromosome 22 and the mutation of NF2 and SMARCB1 in 26 sporadic schwannomas. We found two spinal schwannomas with an identical somatic missense mutation in SMARCB1 exon 9: p.(Arg377His). Both SMARCB1 mutated schwannomas had LOH of 22q and one of them harbored an inactivating mutation of NF2. The p.(Arg377His) change was not found in a series of 28 vestibular schwannomas. Our data indicate that mutations affecting SMARCB1 play a role in the development or progression of a small subset of spinal schwannomas and that biallelic inactivation of SMARCB1 may cooperate with deficiency of NF2 function in schwannoma tumorigenesis according to the "four-hit/three events" mechanism of tumorigenesis that we demonstrated in schwannomatosis-associated schwannomas.

Double somatic SMARCB1 and NF2 mutations in sporadic spinal schwannoma / Paganini I; Capone GL; Vitte J; Sestini R; Putignano AL; Giovannini M; Papi L.. - In: JOURNAL OF NEURO-ONCOLOGY. - ISSN 0167-594X. - STAMPA. - 137:(2018), pp. 33-38. [10.1007/s11060-017-2711-6]

Double somatic SMARCB1 and NF2 mutations in sporadic spinal schwannoma

PAGANINI, IRENE
Formal Analysis
;
CAPONE, GABRIELE LORENZO
Formal Analysis
;
Sestini R
Formal Analysis
;
PUTIGNANO, ANNA LAURA
Formal Analysis
;
Papi L.
Writing – Original Draft Preparation
2018

Abstract

In sporadic schwannomas, inactivation of both copies of the NF2 tumor suppressor gene on 22q is common. Constitutional mutations of SMARCB1 are responsible of schwannomatosis, an inherited tumor predisposition syndrome, characterized by the development of multiple schwannomas. We analysed the frequency of copy number changes on chromosome 22 and the mutation of NF2 and SMARCB1 in 26 sporadic schwannomas. We found two spinal schwannomas with an identical somatic missense mutation in SMARCB1 exon 9: p.(Arg377His). Both SMARCB1 mutated schwannomas had LOH of 22q and one of them harbored an inactivating mutation of NF2. The p.(Arg377His) change was not found in a series of 28 vestibular schwannomas. Our data indicate that mutations affecting SMARCB1 play a role in the development or progression of a small subset of spinal schwannomas and that biallelic inactivation of SMARCB1 may cooperate with deficiency of NF2 function in schwannoma tumorigenesis according to the "four-hit/three events" mechanism of tumorigenesis that we demonstrated in schwannomatosis-associated schwannomas.
2018
137
33
38
Goal 3: Good health and well-being for people
Paganini I; Capone GL; Vitte J; Sestini R; Putignano AL; Giovannini M; Papi L.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1114389
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 7
social impact