Genomic analysis in short- and long-term patients with malignant pleura mesothelioma treated with palliative chemotherapy.
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Biomarkers, Tumor
/ genetics
Electron Transport Complex III
/ genetics
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
/ drug effects
Genomics
/ methods
Guanine Nucleotide Exchange Factors
/ genetics
Humans
Lung Neoplasms
/ drug therapy
Male
Mesothelioma
/ drug therapy
Mesothelioma, Malignant
Mutation
Palliative Care
Pleural Neoplasms
/ drug therapy
Prognosis
Proteoglycans
/ genetics
Retrospective Studies
Survival Rate
Genetic mutations
Malignant pleural mesothelioma
Mitochondrial metabolism
Palliative chemotherapy
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
28
12
2019
accepted:
18
03
2020
pubmed:
28
4
2020
medline:
11
11
2020
entrez:
28
4
2020
Statut:
ppublish
Résumé
Malignant pleural mesothelioma (MPM) is an aggressive tumour with poor prognosis. The aim of this study was to identify genetic mutations associated with poor or extended survival in patients who received palliative chemotherapy. A total of 720 patients diagnosed with MPM between 2005 and 2015 were identified. Overall survival (OS) was longer than 30 months from diagnosis for 27 patients. Twelve of 27 (44%) of the pleural biopsies from long-term survivors were retrieved and matched with 12 biopsies from patients who survived less than 12 months; one biopsy was then excluded for poor DNA quality. A total of 11 patients had a mean OS of 5.5 months, whereas 12 patients lived more than 30 months (mean OS: 55.8 ± 25). Mutational analysis identified 428 alterations; of which, 148, classified as somatic and functional, were considered further. Among these, 85% were missense variants, 8% were variants causing a stop gain and 6% were splice variants. Loss-of-function mutations in UQCRC1 were significantly associated with reduced survival in patients with MPM (p = 0.027), while a higher frequency of mutations in MXRA5 and RAPGEF6 was registered in long-term survivors. This is the first study evaluating the relationship between the mutational profile and outcome in patients with MPM after palliative chemotherapy. UQCRC1 codes for cytochrome b-c1 complex subunit 1 which plays a fundamental role in normal mitochondrial functions and in cell metabolism. Recent studies described UQCRC1 deregulation in other cancers. Our results suggest a possible role for mitochondrial metabolism in the biology of mesothelioma.
Sections du résumé
BACKGROUND
Malignant pleural mesothelioma (MPM) is an aggressive tumour with poor prognosis. The aim of this study was to identify genetic mutations associated with poor or extended survival in patients who received palliative chemotherapy.
METHODS
A total of 720 patients diagnosed with MPM between 2005 and 2015 were identified. Overall survival (OS) was longer than 30 months from diagnosis for 27 patients. Twelve of 27 (44%) of the pleural biopsies from long-term survivors were retrieved and matched with 12 biopsies from patients who survived less than 12 months; one biopsy was then excluded for poor DNA quality.
RESULTS
A total of 11 patients had a mean OS of 5.5 months, whereas 12 patients lived more than 30 months (mean OS: 55.8 ± 25). Mutational analysis identified 428 alterations; of which, 148, classified as somatic and functional, were considered further. Among these, 85% were missense variants, 8% were variants causing a stop gain and 6% were splice variants. Loss-of-function mutations in UQCRC1 were significantly associated with reduced survival in patients with MPM (p = 0.027), while a higher frequency of mutations in MXRA5 and RAPGEF6 was registered in long-term survivors.
CONCLUSION
This is the first study evaluating the relationship between the mutational profile and outcome in patients with MPM after palliative chemotherapy. UQCRC1 codes for cytochrome b-c1 complex subunit 1 which plays a fundamental role in normal mitochondrial functions and in cell metabolism. Recent studies described UQCRC1 deregulation in other cancers. Our results suggest a possible role for mitochondrial metabolism in the biology of mesothelioma.
Identifiants
pubmed: 32339978
pii: S0959-8049(20)30143-X
doi: 10.1016/j.ejca.2020.03.002
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Guanine Nucleotide Exchange Factors
0
MXRA5 protein, human
0
Proteoglycans
0
RAPGEF6 protein, human
0
Electron Transport Complex III
EC 7.1.1.8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104-111Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement None declared.