Publications

Authors:

Simbolo, Michele; Fassan, Matteo; Ruzzenente, Andrea; Mafficini, Andrea; Wood, Ld; Corbo, Vincenzo; Melisi, Davide; Malleo, Giuseppe; Vicentini, Caterina; Malpeli, Giorgio; Antonello, D; Sperandio, Nicola; Capelli, Paola; Tomezzoli, Anna; Iacono, Calogero; Lawlor, Rita Teresa; Bassi, Claudio; Hruban, Rh; Guglielmi, Alfredo; Tortora, Giampaolo; de Braud, F; Scarpa, Aldo

Title:

Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups

Year:

2014

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

Sì

Name of journal:

ONCOTARGET

ISSN of journal:

1949-2553

N° Volume:

5

Number or Folder:

9

Page numbers:

2839-2852

Keyword:

cholangiocarcinoma, next-generation sequencing, molecular subclassification, target therapy, multigene mutational panels

Short description of contents:

One-hundred-fifty-three biliary cancers, including 70 intrahepatic cholangiocarcinomas (ICC), 57 extrahepatic cholangiocarcinomas (ECC) and 26 gallbladder carcinomas (GBC) were assessed for mutations in 56 genes using multigene next-generation sequencing. Expression of EGFR and mTOR pathway genes was investigated by immunohistochemistry. At least one mutated gene was observed in 118/153 (77%) cancers. The genes most frequently involved were KRAS (28%), TP53 (18%), ARID1A (12%), IDH1/2 (9%), PBRM1 (9%), BAP1 (7%), and PIK3CA (7%). IDH1/2 (p=0.0005) and BAP1 (p=0.0097) mutations were characteristic of ICC, while KRAS (p=0.0019) and TP53 (p=0.0019) were more frequent in ECC and GBC. Multivariate analysis identified tumour stage and TP53 mutations as independent predictors of survival. Alterations in chromatin remodeling genes (ARID1A, BAP1, PBRM1, SMARCB1) were seen in 31% of cases. Potentially actionable mutations were seen in 104/153 (68%) cancers: i) KRAS/NRAS/BRAF mutations were found in 34% of cancers; ii) mTOR pathway activation was documented by immunohistochemistry in 51% of cases and by mutations in mTOR pathway genes in 19% of cancers; iii) TGF-ß/Smad signaling was altered in 10.5% cancers; iv) mutations in tyrosine kinase receptors were found in 9% cases. Our study identified molecular subgroups of cholangiocarcinomas that can be explored for specific drug targeting in clinical trials.

Product ID:

81501

Handle IRIS:

11562/733162

Deposited On:

May 30, 2014

Last Modified:

November 15, 2022

Bibliographic citation:

Simbolo, Michele; Fassan, Matteo; Ruzzenente, Andrea; Mafficini, Andrea; Wood, Ld; Corbo, Vincenzo; Melisi, Davide; Malleo, Giuseppe; Vicentini, Caterina; Malpeli, Giorgio; Antonello, D; Sperandio, Nicola; Capelli, Paola; Tomezzoli, Anna; Iacono, Calogero; Lawlor, Rita Teresa; Bassi, Claudio; Hruban, Rh; Guglielmi, Alfredo; Tortora, Giampaolo; de Braud, F; Scarpa, Aldo, Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups «ONCOTARGET» , vol. 5 , n. 9 , 2014 , pp. 2839-2852

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