Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma

Abstract The incidence and mortality rates of intrahepatic cholangiocarcinoma have been rising worldwide. Few patients present an early-stage disease that is amenable to curative surgery and after resection, high recurrence rates persist. To identify new independent marker related to aggressive beha...

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Autores principales:	Michele Simbolo, Caterina Vicentini, Andrea Ruzzenente, Matteo Brunelli, Simone Conci, Matteo Fassan, Andrea Mafficini, Borislav Rusev, Vincenzo Corbo, Paola Capelli, Emilio Bria, Serena Pedron, Giona Turri, Rita T. Lawlor, Giampaolo Tortora, Claudio Bassi, Alfredo Guglielmi, Aldo Scarpa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/43514a3462ab48c3877101c0b0918453
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spelling	oai:doaj.org-article:43514a3462ab48c3877101c0b09184532021-12-02T11:40:46ZGenetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma10.1038/s41598-018-25669-12045-2322https://doaj.org/article/43514a3462ab48c3877101c0b09184532018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25669-1https://doaj.org/toc/2045-2322Abstract The incidence and mortality rates of intrahepatic cholangiocarcinoma have been rising worldwide. Few patients present an early-stage disease that is amenable to curative surgery and after resection, high recurrence rates persist. To identify new independent marker related to aggressive behaviour, two prognostic groups of patient were selected and divided according to prognostic performance. All patients alive at 36 months were included in good prognostic performers, while all patients died due to disease within 36 months in poor prognostic performers. Using high-coverage target sequencing we analysed principal genetic alterations in two groups and compared results to clinical data. In the 33 cases included in poor prognosis group, TP53 was most mutated gene (p = 0.011) and exclusively present in these cases. Similarly, ARID1A was exclusive of this group (p = 0.024). TP53 and ARID1A are mutually exclusive in this study. Statistical analysis showed mutations in TP53 and ARID1A genes and amplification of MET gene as independent predictors of poor prognosis (TP53, p = 0.0031, ARID1A, p = 0.0007, MET, p = 0.0003 in Cox analysis). LOH in PTEN was also identified as marker of disease recurrence (p = 0.04) in univariate analysis. This work improves our understanding of aggressiveness related to this tumour type and has identified novel prognostic markers of clinical outcome.Michele SimboloCaterina VicentiniAndrea RuzzenenteMatteo BrunelliSimone ConciMatteo FassanAndrea MafficiniBorislav RusevVincenzo CorboPaola CapelliEmilio BriaSerena PedronGiona TurriRita T. LawlorGiampaolo TortoraClaudio BassiAlfredo GuglielmiAldo ScarpaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michele Simbolo Caterina Vicentini Andrea Ruzzenente Matteo Brunelli Simone Conci Matteo Fassan Andrea Mafficini Borislav Rusev Vincenzo Corbo Paola Capelli Emilio Bria Serena Pedron Giona Turri Rita T. Lawlor Giampaolo Tortora Claudio Bassi Alfredo Guglielmi Aldo Scarpa Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma
description	Abstract The incidence and mortality rates of intrahepatic cholangiocarcinoma have been rising worldwide. Few patients present an early-stage disease that is amenable to curative surgery and after resection, high recurrence rates persist. To identify new independent marker related to aggressive behaviour, two prognostic groups of patient were selected and divided according to prognostic performance. All patients alive at 36 months were included in good prognostic performers, while all patients died due to disease within 36 months in poor prognostic performers. Using high-coverage target sequencing we analysed principal genetic alterations in two groups and compared results to clinical data. In the 33 cases included in poor prognosis group, TP53 was most mutated gene (p = 0.011) and exclusively present in these cases. Similarly, ARID1A was exclusive of this group (p = 0.024). TP53 and ARID1A are mutually exclusive in this study. Statistical analysis showed mutations in TP53 and ARID1A genes and amplification of MET gene as independent predictors of poor prognosis (TP53, p = 0.0031, ARID1A, p = 0.0007, MET, p = 0.0003 in Cox analysis). LOH in PTEN was also identified as marker of disease recurrence (p = 0.04) in univariate analysis. This work improves our understanding of aggressiveness related to this tumour type and has identified novel prognostic markers of clinical outcome.
format	article
author	Michele Simbolo Caterina Vicentini Andrea Ruzzenente Matteo Brunelli Simone Conci Matteo Fassan Andrea Mafficini Borislav Rusev Vincenzo Corbo Paola Capelli Emilio Bria Serena Pedron Giona Turri Rita T. Lawlor Giampaolo Tortora Claudio Bassi Alfredo Guglielmi Aldo Scarpa
author_facet	Michele Simbolo Caterina Vicentini Andrea Ruzzenente Matteo Brunelli Simone Conci Matteo Fassan Andrea Mafficini Borislav Rusev Vincenzo Corbo Paola Capelli Emilio Bria Serena Pedron Giona Turri Rita T. Lawlor Giampaolo Tortora Claudio Bassi Alfredo Guglielmi Aldo Scarpa
author_sort	Michele Simbolo
title	Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma
title_short	Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma
title_full	Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma
title_fullStr	Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma
title_full_unstemmed	Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma
title_sort	genetic alterations analysis in prognostic stratified groups identified tp53 and arid1a as poor clinical performance markers in intrahepatic cholangiocarcinoma
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/43514a3462ab48c3877101c0b0918453
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_version_	1718395512719147008

Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma

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