Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma
-
Published:2022-11-05
Issue:1
Volume:12
Page:
-
ISSN:2045-2322
-
Container-title:Scientific Reports
-
language:en
-
Short-container-title:Sci Rep
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
Abstract
AbstractIDH1-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.
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
Reference29 articles.
1. Sia, D., Villanueva, A., Friedman, S. L. & Llovet, J. M. Liver cancer cell of origin, molecular class, and effects on patient prognosis. Gastroenterology 152, 745–761 (2017). 2. Khan, S. A., Thomas, H. C., Davidson, B. R. & Taylor-Robinson, S. D. Cholangiocarcinoma. Lancet 366(9493), 1303–1314 (2005). 3. Petrick, J. et al. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: A population-based study in SEERmedicare. PLoS ONE 12, 10 (2017). 4. Howlader, N., Noone, A.M., Krapcho, M., et al. (Eds.) SEER Cancer Statistics Review, 1975-2013, National Cancer Institute. Bethesda, MD, Based on November 2015 SEER Data Submission, Posted to the SEER Web Site 5. April 2016. http://seer.cancer.gov/csr/1975_2013/. Accessed 10 Dec 2016 (2016).
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|