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

• Published in: Scientific reports Vol. 12; no. 1; pp. 18775 - 12
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-11-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/1504; 631/67/69; Bile Duct Neoplasms - pathology; Bile Ducts, Intrahepatic - pathology; BRCA2 protein; Breast cancer; Carrier Proteins - genetics; Cholangiocarcinoma; Cholangiocarcinoma - pathology; Fibroblast growth factor receptor 2; Genomic analysis; Humanities and Social Sciences; Humans; Isocitrate Dehydrogenase - genetics; Metastases; multidisciplinary; Mutation; Mutation rates; p53 Protein; Patients; Prognosis; Science; Science (multidisciplinary); Survival; Survival analysis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-22543-z

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.