학술논문
MGMT inactivation as a new biomarker in patients with advanced biliary tract cancers
Document Type
article
Author
Monica Niger; Federico Nichetti; Andrea Casadei‐Gardini; Federica Morano; Chiara Pircher; Elena Tamborini; Federica Perrone; Matteo Canale; Daniel B. Lipka; Andrea Vingiani; Luca Agnelli; Anna Dobberkau; Jennifer Hüllein; Felix Korell; Christoph E. Heilig; Sara Pusceddu; Francesca Corti; Michele Droz; Paola Ulivi; Michele Prisciandaro; Maria Antista; Marta Bini; Laura Cattaneo; Massimo Milione; Hanno Glimm; Bruno C. Köhler; Giancarlo Pruneri; Daniel Hübschmann; Stefan Fröhling; Vincenzo Mazzaferro; Filippo Pietrantonio; Maria Di Bartolomeo; Filippo deBraud
Source
Molecular Oncology, Vol 16, Iss 14, Pp 2733-2746 (2022)
Subject
Language
English
ISSN
1878-0261
1574-7891
1574-7891
Abstract
Biliary tract cancers (BTCs) have poor prognosis and limited therapeutic options. The impact of O6‐methylguanine‐DNA methyltransferase (MGMT) inactivation in advanced BTC patients is not established. We investigated the prevalence, prognostic, and predictive impact of MGMT inactivation in two multicenter cohorts. MGMT inactivation was assessed through PCR and immunohistochemistry (IHC) in an Italian cohort; the results were then externally validated using RNA sequencing (RNA‐seq) data from the BTC subcohort of the Molecularly Aided Stratification for Tumor Eradication Research (MASTER) precision oncology program of the National Center for Tumor Diseases Heidelberg and the German Cancer Consortium. Among 164 Italian cases, 18% presented MGMT promoter hypermethylation (> 14%) and 73% had negative MGMT protein expression. Both were associated with worse overall survival (OS; HR 2.31; P