MGMT inactivation as a new biomarker in patients with advanced biliary tract cancers.
Mol Oncol
; 16(14): 2733-2746, 2022 07.
Article
in En
| MEDLINE
| ID: mdl-35621918
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 < 0.001 and HR 1.99, P = 0.012, respectively). In the MASTER cohort, patients with lower MGMT mRNA expression showed significantly poorer OS (median OS [mOS] 20.4 vs 31.7 months, unadjusted HR 1.89; P = 0.043). Our results suggest that MGMT inactivation is a frequent epigenetic alteration in BTC, with a significant prognostic impact, and provide the rationale to explore DNA-damaging agents in MGMT-inactivated BTCs.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bile Duct Neoplasms
/
Biliary Tract Neoplasms
Type of study:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Mol Oncol
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2022
Document type:
Article
Affiliation country:
Italy