Open AccessAKT 1 and BRAF mutations in pediatric aggressive fibromatosis
Author(s) -
Meazza Cristina,
Belfiore Antonino,
Busico Adele,
Settanni Giulio,
Paielli Nicholas,
Cesana Luca,
Ferrari Andrea,
Chiaravalli Stefano,
Massimino Maura,
Gronchi Alessandro,
Colombo Chiara,
Pilotti Silvana,
Perrone Federica
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.669
Subject(s) - sanger sequencing , protein kinase b , mutation , cancer research , medicine , adenomatous polyposis coli , oncology , silent mutation , gene , biology , genetics , cancer , phosphorylation , colorectal cancer , missense mutation
Aside from the CTNNB 1 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. CTNNB 1 , APC , AKT 1 , BRAF TP 53 , 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 AF s. The prognostic value of CTNNB 1 , AKT 1 , 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 CTNNB 1 mutation (64%), pediatric AF showed AKT 1 (31%), BRAF (19%), and TP 53 (9%) mutations, whereas only the CTNNB 1 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 CTNNB 1 but also AKT 1 and BRAF . This intriguing finding may have clinical implications and warrants further investigations.