Journal Article

Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma

Fabregat-Franco, Carles, Scartozzi, Mario, Aldrighetti, Luca, Niger, Monica, Fassan, Matteo, Nichetti, Federico, Cappetta, Alessandro, Lonardi, Sara, Rizzato, Mario, Fornaro, Lorenzo, Aprile, Giuseppe, Pretta, Andrea, Casadei-Gardini, Andrea, Lai, Eleonora, Cascinu, Stefano, Burgio, Valentina, De Braud, Filippo, Rapposelli, Ilario Giovanni, Ratti, Francesca, Simionato, Francesca, De Cobelli, Francesco, Macarulla, Teresa, Pedica, Federica, Verdaguer, Helena, Rimini, Margherita

2022

Overview

IDH1 -mutated cholangiocarcinomas (CCAs) are an interesting group of neoplasia with particular behavior and therapeutic implications. The aim of the present work is to highlight the differences characterizing IDH1 m and IDH1 wt CCAs in terms of genomic landscape. 284 patients with iCCA treated for resectable, locally advanced or metastatic disease were selected and studied with the FOUNDATION Cdx technology. A comparative genomic analysis and survival analyses for the most relevant altered genes were performed between IDH1 m and IDH1 wt patients. Overall, 125 patients were IDH1 m and 122 IDH1 wt. IDH1 m patients showed higher mutation rates compared to IDH1 wt in CDKN2B and lower mutation rates in several genes including TP53 , FGFR2 , BRCA2 , ATM , MAP3K1 , NOTCH2 , ZNF703 , CCND1 , NBN , NF1 , MAP3 KI3 , and RAD21 . At the survival analysis, IDH1 m and IDH1 wt patients showed no statistically differences in terms of survival outcomes, but a trend in favor of IDH1wt patients was observed. Differences in prognostic values of the most common altered genes were reported. In surgical setting, in IDH1 m group the presence of CDKN2A and CDKN2B mutations negatively impact DFS, whereas the presence of CDKN2A, CDKN2B , and PBRM1 mutations negatively impact OS. In advanced setting, in the IDH1 m group, the presence of KRAS/NRAS and TP53 mutations negatively impact PFS, whereas the presence of TP53 and PIK3CA mutations negatively impact OS; in the IDH1wt group, only the presence of MTAP mutation negatively impact PFS, whereas the presence of TP53 mutation negatively impact OS. We highlighted several molecular differences with distinct prognostic implications between IDH1 m and IDH1 wt patients.

• Publisher: Springer Science and Business Media LLC,Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/67/1504 / 631/67/69 / Anomalies cromosòmiques / Bile Duct Neoplasms / Bile Duct Neoplasms - pathology / Bile Ducts, Intrahepatic / Bile Ducts, Intrahepatic - pathology / BRCA2 protein / Breast cancer / Carrier Proteins / Carrier Proteins - genetics / Cholangiocarcinoma / Cholangiocarcinoma - pathology / Conductes biliars - Càncer / fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS] / Fibroblast growth factor receptor 2 / Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES] / Genomic analysis / Humanities and Social Sciences / Humans / Isocitrate Dehydrogenase / Isocitrate Dehydrogenase - genetics / Medicine / Metastases / multidisciplinary / Mutation / Mutation rates / neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias del tracto biliar::neoplasias de los conductos biliares [ENFERMEDADES] / neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma::colangiocarcinoma [ENFERMEDADES] / Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Cholangiocarcinoma [DISEASES] / Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Biliary Tract Neoplasms::Bile Duct Neoplasms [DISEASES] / p53 Protein / Patients / Prognosis / Q / R / Science / Science (multidisciplinary) / Survival / Survival analysis