title: AKT1 and BRAF mutations in pediatric aggressive fibromatosis.
abstract: Aside from the CTNNB1 and adenomatous polyposis coli (APC) mutations, the genetic profile of pediatric aggressive fibromatosis (AF) has remained poorly characterized. The aim of this study was to shed more light on the mutational spectrum of pediatric AF, comparing it with its adult counterpart, with a view to identifying biomarkers for use as prognostic factors or new potential therapeutic targets. CTNNB1, APC, AKT1, BRAF TP53, and RET Sanger sequencing and next-generation sequencing (NGS) with the 50-gene Ion AmpliSeq Cancer Hotspot Panel v2 were performed on formalin-fixed samples from 28 pediatric and 33 adult AFs. The prognostic value of CTNNB1, AKT1, and BRAF mutations in pediatric AF patients was investigated. Recurrence-free survival (RFS) curves were estimated with the Kaplan-Meier method and statistical comparisons were drawn using the log-rank test. In addition to the CTNNB1 mutation (64%), pediatric AF showed AKT1 (31%), BRAF (19%), and TP53 (9%) mutations, whereas only the CTNNB1 mutation was found in adult AF. The polymorphism Q472H VEGFR was identified in both pediatric (56%) and adult (40%) AF. Our results indicate that the mutational spectrum of pediatric AF is more complex than that of adult AF, with multiple gene mutations involving not only CTNNB1 but also AKT1 and BRAF. This intriguing finding may have clinical implications and warrants further investigations.
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Meazza
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Belfiore
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Busico
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Settanni
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Paielli
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cesana
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Chiaravalli
authors.affiliation: Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Massimino
authors.affiliation: Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gronchi
authors.affiliation: Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Perrone
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D018222:Desmoid Tumors / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C494918:AKT1 protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT1; BRAF; CTNNB1, TP53; pediatric aggressive fibromatosis