Cancers, Vol. 12, Pages 2503: Pre- and Post-Zygotic TP53 De Novo Mutations in SHH-Medulloblastoma

Cancers, Vol. 12, Pages 2503: Pre- and Post-Zygotic TP53 De Novo Mutations in SHH-Medulloblastoma Cancers doi: 10.3390/cancers12092503 Authors: Jacopo Azzollini Elisabetta Schiavello Francesca Romana Buttarelli Carlo Alfredo Clerici Laura Tizzoni Giovanna De Vecchi Fabio Capra Federica Pisati Veronica Biassoni Letterio Runza Giorgio Carrabba Felice Giangaspero Maura Massimino Valeria Pensotti Siranoush Manoukian Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder caused by mutations in the TP53 gene, predisposing to a wide spectrum of early-onset cancers, including brain tumors. In medulloblastoma patients, the role of TP53 has been extensively investigated, though the prevalence of de novo mutations has not been addressed. We characterized TP53 mutations in a monocentric cohort of consecutive Sonic Hedgehog (SHH)-activated medulloblastoma patients. Germline testing was offered based on tumor p53 immunostaining positivity. Among 24 patients, three (12.5%) showed tumor p53 overexpression, of whom two consented to undergo germline testing and resulted as carriers of TP53 mutations. In the first case, family history was uneventful and the mutation was not found in either of the parents. The second patient, with a family history suggestive of LFS, unexpectedly resulted as a carrier of the mosaic mutation c.742=/C>T p.(Arg248=/Trp). The allele frequency was 26% in normal tissues and 42–77% in tumor specimens. Lo...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research