Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 11 2022
05 11 2022
Historique:
received:
18
07
2022
accepted:
17
10
2022
entrez:
6
11
2022
pubmed:
6
11
2022
medline:
9
11
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36335135
doi: 10.1038/s41598-022-22543-z
pii: 10.1038/s41598-022-22543-z
pmc: PMC9637171
doi:
Substances chimiques
ZNF703 protein, human
0
Carrier Proteins
0
IDH1 protein, human
EC 1.1.1.42.
Isocitrate Dehydrogenase
EC 1.1.1.41
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
18775Informations de copyright
© 2022. The Author(s).
Références
Lancet Oncol. 2020 Jun;21(6):796-807
pubmed: 32416072
Oncol Lett. 2020 Apr;19(4):3101-3110
pubmed: 32256810
Oncologist. 2014 Mar;19(3):235-42
pubmed: 24563076
Lancet. 2005 Oct 8;366(9493):1303-14
pubmed: 16214602
Cancers (Basel). 2021 Oct 15;13(20):
pubmed: 34680318
Histol Histopathol. 2015 Oct;30(10):1155-60
pubmed: 26147657
Nat Genet. 2015 Sep;47(9):1003-10
pubmed: 26258846
Clin Cancer Res. 2016 Apr 15;22(8):1837-42
pubmed: 26819452
Ann Oncol. 2016 Apr;27(4):599-608
pubmed: 27005468
Jpn J Clin Oncol. 2020 Sep 28;50(10):1117-1125
pubmed: 32533190
Ann Surg Oncol. 2016 May;23(5):1699-707
pubmed: 26717940
Cancer Cell. 2018 Aug 13;34(2):186-195
pubmed: 29805076
J Gastrointest Oncol. 2019 Aug;10(4):751-765
pubmed: 31392056
PLoS One. 2017 Oct 19;12(10):e0186643
pubmed: 29049401
Cancer. 2016 Dec 15;122(24):3838-3847
pubmed: 27622582
Cell Rep. 2017 Mar 14;18(11):2780-2794
pubmed: 28297679
Clin Cancer Res. 2018 Sep 1;24(17):4154-4161
pubmed: 29848569
Gastroenterology. 2017 Mar;152(4):745-761
pubmed: 28043904
PLoS One. 2014 Dec 23;9(12):e115383
pubmed: 25536104
Ann Med. 2019 Feb;51(1):28-40
pubmed: 30592434
Hepatology. 2021 Sep;74(3):1429-1444
pubmed: 33765338
Discov Med. 2016 May;21(117):373-80
pubmed: 27355333
Oncotarget. 2014 May 15;5(9):2839-52
pubmed: 24867389
Expert Rev Gastroenterol Hepatol. 2021 Dec;15(12):1367-1383
pubmed: 34669536
Future Oncol. 2013 Dec;9(12):1923-35
pubmed: 24295421