PBRM1 loss is a late event during the development of cholangiocarcinoma

Nicola Veronese, Seung-Mo Hong, Laura D. Wood, Robert A. Anders, Nicola Veronese, Alessia Nottegar, Antonio Pea, Jin He, Matthew J. Weiss, Claudio Luchini, Scott A. Robertson, Matthäus Felsenstein, Seung-Mo Hong, Scott A. Robertson, Aldo Scarpa, Aldo Scarpa, Paola Capelli, Pedram Argani, Payal Kapur

Risultato della ricerca: Articlepeer review

15 Citazioni (Scopus)

Abstract

Aims: Somatic mutations in genes encoding chromatin remodellers have been reported recently in several cancer types, including approximately half of cholangiocarcinomas. One of the most commonly mutated chromatin remodellers in cholangiocarcinoma is the Polybromo-1 (PBRM1) gene located on chromosome 3p21, which encodes a subunit of the SWI/SNF complex. The aim of this study was to determine the timing of PBRM1 mutations in biliary carcinogenesis. Methods and results: In order to accomplish this goal, we used immunohistochemistry to assess PBRM1 protein expression in a series of precursor lesions and invasive biliary carcinomas. Previous studies have correlated loss of protein expression on immunohistochemistry with inactivating mutations in this tumour suppressor gene. We found that PBRM1 loss occurred in approximately 26% of invasive cancers, but PBRM1 expression was retained in all biliary intra-epithelial neoplasia (BilIN) specimens, including 25 intrahepatic BilINs and 19 gallbladder BilINs. Conclusions: These findings indicate that PBRM1 mutation (and resultant loss of expression) is a late event during biliary carcinogenesis. In addition, we confirm a lack of prognostic significance of PBRM1 status in invasive intrahepatic cholangiocarcinoma. This study provides important insights into the basic mechanisms of chromatin remodelling genes in carcinogenesis. © 2017 John Wiley & Sons Ltd
Lingua originaleEnglish
pagine (da-a)375-382
Numero di pagine8
RivistaHistopathology
Volume71
Stato di pubblicazionePublished - 2017

All Science Journal Classification (ASJC) codes

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