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

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 IDH1m and IDH1wt CCAs in terms of genomic landscape. 284 patients with iCCA treated for rese...

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Autores principales: Rimini, Margherita, Fabregat-Franco, Carles, Burgio, Valentina, Lonardi, Sara, Niger, Monica, Scartozzi, Mario, Rapposelli, Ilario Giovanni, Aprile, Giuseppe, Ratti, Francesca, Pedica, Federica, Verdaguer, Helena, Rizzato, Mario, Nichetti, Federico, Lai, Eleonora, Cappetta, Alessandro, Macarulla, Teresa, Fassan, Matteo, De Braud, Filippo, Pretta, Andrea, Simionato, Francesca, De Cobelli, Francesco, Aldrighetti, Luca, Fornaro, Lorenzo, Cascinu, Stefano, Casadei-Gardini, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637171/
https://www.ncbi.nlm.nih.gov/pubmed/36335135
http://dx.doi.org/10.1038/s41598-022-22543-z
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author Rimini, Margherita
Fabregat-Franco, Carles
Burgio, Valentina
Lonardi, Sara
Niger, Monica
Scartozzi, Mario
Rapposelli, Ilario Giovanni
Aprile, Giuseppe
Ratti, Francesca
Pedica, Federica
Verdaguer, Helena
Rizzato, Mario
Nichetti, Federico
Lai, Eleonora
Cappetta, Alessandro
Macarulla, Teresa
Fassan, Matteo
De Braud, Filippo
Pretta, Andrea
Simionato, Francesca
De Cobelli, Francesco
Aldrighetti, Luca
Fornaro, Lorenzo
Cascinu, Stefano
Casadei-Gardini, Andrea
author_facet Rimini, Margherita
Fabregat-Franco, Carles
Burgio, Valentina
Lonardi, Sara
Niger, Monica
Scartozzi, Mario
Rapposelli, Ilario Giovanni
Aprile, Giuseppe
Ratti, Francesca
Pedica, Federica
Verdaguer, Helena
Rizzato, Mario
Nichetti, Federico
Lai, Eleonora
Cappetta, Alessandro
Macarulla, Teresa
Fassan, Matteo
De Braud, Filippo
Pretta, Andrea
Simionato, Francesca
De Cobelli, Francesco
Aldrighetti, Luca
Fornaro, Lorenzo
Cascinu, Stefano
Casadei-Gardini, Andrea
author_sort Rimini, Margherita
collection PubMed
description 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 IDH1m and IDH1wt 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 IDH1m and IDH1wt patients. Overall, 125 patients were IDH1m and 122 IDH1wt. IDH1m patients showed higher mutation rates compared to IDH1wt in CDKN2B and lower mutation rates in several genes including TP53, FGFR2, BRCA2, ATM, MAP3K1, NOTCH2, ZNF703, CCND1, NBN, NF1, MAP3KI3, and RAD21. At the survival analysis, IDH1m and IDH1wt 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 IDH1m 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 IDH1m 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 IDH1m and IDH1wt patients.
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spelling pubmed-96371712022-11-07 Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma Rimini, Margherita Fabregat-Franco, Carles Burgio, Valentina Lonardi, Sara Niger, Monica Scartozzi, Mario Rapposelli, Ilario Giovanni Aprile, Giuseppe Ratti, Francesca Pedica, Federica Verdaguer, Helena Rizzato, Mario Nichetti, Federico Lai, Eleonora Cappetta, Alessandro Macarulla, Teresa Fassan, Matteo De Braud, Filippo Pretta, Andrea Simionato, Francesca De Cobelli, Francesco Aldrighetti, Luca Fornaro, Lorenzo Cascinu, Stefano Casadei-Gardini, Andrea Sci Rep Article 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 IDH1m and IDH1wt 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 IDH1m and IDH1wt patients. Overall, 125 patients were IDH1m and 122 IDH1wt. IDH1m patients showed higher mutation rates compared to IDH1wt in CDKN2B and lower mutation rates in several genes including TP53, FGFR2, BRCA2, ATM, MAP3K1, NOTCH2, ZNF703, CCND1, NBN, NF1, MAP3KI3, and RAD21. At the survival analysis, IDH1m and IDH1wt 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 IDH1m 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 IDH1m 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 IDH1m and IDH1wt patients. Nature Publishing Group UK 2022-11-05 /pmc/articles/PMC9637171/ /pubmed/36335135 http://dx.doi.org/10.1038/s41598-022-22543-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Rimini, Margherita
Fabregat-Franco, Carles
Burgio, Valentina
Lonardi, Sara
Niger, Monica
Scartozzi, Mario
Rapposelli, Ilario Giovanni
Aprile, Giuseppe
Ratti, Francesca
Pedica, Federica
Verdaguer, Helena
Rizzato, Mario
Nichetti, Federico
Lai, Eleonora
Cappetta, Alessandro
Macarulla, Teresa
Fassan, Matteo
De Braud, Filippo
Pretta, Andrea
Simionato, Francesca
De Cobelli, Francesco
Aldrighetti, Luca
Fornaro, Lorenzo
Cascinu, Stefano
Casadei-Gardini, Andrea
Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma
title Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma
title_full Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma
title_fullStr Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma
title_full_unstemmed Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma
title_short Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma
title_sort molecular profile and its clinical impact of idh1 mutated versus idh1 wild type intrahepatic cholangiocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637171/
https://www.ncbi.nlm.nih.gov/pubmed/36335135
http://dx.doi.org/10.1038/s41598-022-22543-z
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