Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Article Molecular Profile of Liver Tumors in the Setting of Fontan-Associated Liver Disease

Paola Francalanci
* ORCID logo ,
Isabella Giovannoni
,
Chantal Tancredi
,
Maria Giulia Gagliardi
,
Rosalinda Palmieri
,
Gianluca Brancaccio
,
Marco Spada
,
Giuseppe Maggiore
ORCID logo ,
Andrea Pietrobattista
ORCID logo ,
Lidia Monti
,
Aurora Castellano
,
Maria Cristina Giustiniani
,
Andrea Onetti Muda
ORCID logo ,
Rita Alaggio
Version 1 : Received: 5 September 2023 / Approved: 5 September 2023 / Online: 6 September 2023 (10:13:28 CEST)

How to cite: Francalanci, P.; Giovannoni, I.; Tancredi, C.; Gagliardi, M. G.; Palmieri, R.; Brancaccio, G.; Spada, M.; Maggiore, G.; Pietrobattista, A.; Monti, L.; Castellano, A.; Giustiniani, M. C.; Onetti Muda, A.; Alaggio, R. Article Molecular Profile of Liver Tumors in the Setting of Fontan-Associated Liver Disease. Preprints 2023, 2023090355. https://doi.org/10.20944/preprints202309.0355.v1 Francalanci, P.; Giovannoni, I.; Tancredi, C.; Gagliardi, M. G.; Palmieri, R.; Brancaccio, G.; Spada, M.; Maggiore, G.; Pietrobattista, A.; Monti, L.; Castellano, A.; Giustiniani, M. C.; Onetti Muda, A.; Alaggio, R. Article Molecular Profile of Liver Tumors in the Setting of Fontan-Associated Liver Disease. Preprints 2023, 2023090355. https://doi.org/10.20944/preprints202309.0355.v1

Abstract

Purpose: To analyze the genetic and molecular profile of liver nodules in the context of Fontan-associated liver disease (FALD) with the aim of identifying possible biomarkers for predictive outcome and personalized therapy. Methods: this retrospective monocentric study included 9 patients who developed FALD in the context of congestive cirrhosis:1 regenerative nodular hyperplasia, 2 hepatic adenomas (HA) and 4 hepatocellular carcinoma (HCC), 1 fibrolamellar carcinoma (FLC) and 1 intrahepatic cholangiocarcinoma (ICC). The lesions were analyzed by histology and immunohistochemistry (b-catenin, glypican 3, glutamine synthetase and SOX9). To study the molecular profile of neoplastic FALD, targeted NGS was performed on DNA and RNA from formalin-fixed paraffin embedded neoplastic liver tissue of 1 HA, 2 HCCs, 1 FLC and 1 ICC. Results: Molecular analysis showed 3 patients with copy number alteration involving FGFR3, and one patient with a hotspot mutation on CTNNB1 and NRAS genes. All 5 patients showed a tumor mutational burden ranging from low to intermediate. Variants of unknown significance in GNAS were present in 2 HCC and 1 ICC. The single FLC had a DNAJB1-PRKACA fusion. Conclusions: The molecular results seem to be consistent with a peculiar molecular profile of the malignant FALD which may be useful for new target therapies for HCC/ICC in FALD.

Keywords

FALD; hepatocellular carcinoma; cholangiocarcinoma; NGS; FGFRs genes; GNAS and TMB

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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