Tert promoter mutation as an independent ...
Document type :
Article dans une revue scientifique: Article original
DOI :
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Title :
Tert promoter mutation as an independent prognostic marker for poor prognosis mapk inhibitors-treated melanoma
Author(s) :
Blateau, Pauline [Auteur]
Coyaud, Etienne-Marie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Laurent, Estelle [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Beganton, Benoit [Auteur]
Ducros, Vincent [Auteur]
Chauchard, Geraldine [Auteur]
Vendrell, Julie A. [Auteur]
Solassol, Jerome [Auteur]
Coyaud, Etienne-Marie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Laurent, Estelle [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Beganton, Benoit [Auteur]
Ducros, Vincent [Auteur]
Chauchard, Geraldine [Auteur]
Vendrell, Julie A. [Auteur]
Solassol, Jerome [Auteur]
Journal title :
Cancers
Volume number :
12
Pages :
2224
Publisher :
MDPI
Publication date :
2020-08-09
ISSN :
2072-6694
English keyword(s) :
co-occurring mutation
TERT promoter
prognosis factor
targeted therapies
melanoma
BRAFV600
TERT promoter
prognosis factor
targeted therapies
melanoma
BRAFV600
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Although the development of mitogen-activated protein kinase (MAPK) inhibitors has greatly improved the prognosis of BRAF(V600) cutaneous melanomas, the identification of molecular indicators for mutated patients at risk ...
Show more >Although the development of mitogen-activated protein kinase (MAPK) inhibitors has greatly improved the prognosis of BRAF(V600) cutaneous melanomas, the identification of molecular indicators for mutated patients at risk of early progression remains a major issue. Using an amplicon-based next-generation-sequencing (NGS) assay that targets cancer-related genes, we investigated co-occurring alterations in 89 melanoma samples. We analyzed both their association with clinicopathological variables and clinical significance in terms of progression-free survival (PFS) and overall survival (OS) according to BRAF genotyping. Among co-occurring mutations, TERT promoter was the most frequently mutated gene. Although no significant difference in PFS was observed in the presence or absence of co-occurring alterations to BRAF(V600), there was a trend of longer PFS for patients harboring TERT c.-124C>T mutation. Of most interest, this mutation is an independent marker of good prognosis in subgroups of patients with poor prognosis (presence of brain metastasis and elevated level of lactate dehydrogenase, LDH). Moreover, combination of elevated LDH level, presence of brain metastasis, and TERT c.-124C>T mutation was identified as the best fit model for predicting clinical outcome. Our work revealed the potential interest of c.-124C>T status determination in order to refine the prognosis of BRAF(V600) melanoma under mitogen-activated protein kinase (MAPK) inhibitors.Show less >
Show more >Although the development of mitogen-activated protein kinase (MAPK) inhibitors has greatly improved the prognosis of BRAF(V600) cutaneous melanomas, the identification of molecular indicators for mutated patients at risk of early progression remains a major issue. Using an amplicon-based next-generation-sequencing (NGS) assay that targets cancer-related genes, we investigated co-occurring alterations in 89 melanoma samples. We analyzed both their association with clinicopathological variables and clinical significance in terms of progression-free survival (PFS) and overall survival (OS) according to BRAF genotyping. Among co-occurring mutations, TERT promoter was the most frequently mutated gene. Although no significant difference in PFS was observed in the presence or absence of co-occurring alterations to BRAF(V600), there was a trend of longer PFS for patients harboring TERT c.-124C>T mutation. Of most interest, this mutation is an independent marker of good prognosis in subgroups of patients with poor prognosis (presence of brain metastasis and elevated level of lactate dehydrogenase, LDH). Moreover, combination of elevated LDH level, presence of brain metastasis, and TERT c.-124C>T mutation was identified as the best fit model for predicting clinical outcome. Our work revealed the potential interest of c.-124C>T status determination in order to refine the prognosis of BRAF(V600) melanoma under mitogen-activated protein kinase (MAPK) inhibitors.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
INSERM
Université de Lille
Université de Lille
Submission date :
2022-06-15T13:59:49Z
2023-03-07T10:11:19Z
2023-03-07T10:11:19Z
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