Expression and mutational status of treatment-relevant targets and key oncogenes in 123 malignant salivary gland tumours.
J. Cros
,
Emilie Sbidian
(1)
,
Stéphane Hans
(2, 3)
,
H. Roussel
,
Florient Scotté
(4)
,
Eric Tartour
(5)
,
Daniel Brasnu
(3, 4)
,
Pierre Laurent-Puig
(4)
,
P. Bruneval
(6)
,
H. Blons
,
Cécile Badoual
(6, 7)
1
LIC -
Laboratoire d'Investigation Clinique
2 Service d'oto-rhino-laryngologie et chirurgie cervico-faciale [CHU HEGP]
3 LPP - LPP - Laboratoire de Phonétique et Phonologie - UMR 7018
4 HEGP - Hôpital Européen Georges Pompidou [APHP]
5 U753 - Cytokines et Immunologie des Tumeurs Humaines
6 PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire
7 Service d'anatomo-pathologie [CHU HEGP]
2 Service d'oto-rhino-laryngologie et chirurgie cervico-faciale [CHU HEGP]
3 LPP - LPP - Laboratoire de Phonétique et Phonologie - UMR 7018
4 HEGP - Hôpital Européen Georges Pompidou [APHP]
5 U753 - Cytokines et Immunologie des Tumeurs Humaines
6 PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire
7 Service d'anatomo-pathologie [CHU HEGP]
J. Cros
- Fonction : Auteur
Emilie Sbidian
- Fonction : Auteur
- PersonId : 774565
- ORCID : 0000-0002-1267-5270
Stéphane Hans
- Fonction : Auteur
- PersonId : 759159
- IdRef : 18606439X
H. Roussel
- Fonction : Auteur
Daniel Brasnu
- Fonction : Auteur
- PersonId : 844077
H. Blons
- Fonction : Auteur
Cécile Badoual
- Fonction : Auteur
- PersonId : 950072
Résumé
Malignant tumours of the salivary glands (MSGT) are rare and pleomorphic entities. Patients with advanced disease may benefit from targeted therapy; however, specific targets for optimising and personalising treatments are yet to be identified.
Immunohistochemistry for C-KIT, EGFR, HER2, MUC1, phospho-mTOR, androgen/estrogens/progesterone receptors and Ki67 was carried out and evaluated in terms of progression-free and overall survival. High throughput molecular screening of key oncogenes was done in 107 patients using routine diagnostic methods and Sequenom technology.
Several therapy leads were identified, including high levels of HER2 and androgen receptors in salivary duct carcinomas, C-KIT in myoepithelial carcinomas and EGFR in mucoepidermoid carcinomas. Recurrent mutations involving downstream elements of the EGFR pathway were found in HRAS, notably in tumours with a myoepithelial component, and in other key oncogenes (KRAS/NRAS/PI3KCA/BRAF/MAP2K). On the other hand, < 1% of samples had EGFR or HER2 mutations.
Several tumour subtypes overexpressed targets of directed therapies suggesting potential therapy leads. Genotyping results suggest activation downstream of EGFR in 18 of the 107 samples that could be associated with low efficacy of EGFR inhibitors. Other molecules, such as PI3K/MEK or mTOR inhibitors, may have anti-tumour activity in this subgroup. The high mutation rate in HRAS highlights a novel key oncogenic event in MSGT.
Domaines
LinguistiqueFormat du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Expression and mutational status of treatment-relevant targets and key oncogenes in 123 malignant salivary gland tumours.
|
Résumé |
en
Malignant tumours of the salivary glands (MSGT) are rare and pleomorphic entities. Patients with advanced disease may benefit from targeted therapy; however, specific targets for optimising and personalising treatments are yet to be identified.
Immunohistochemistry for C-KIT, EGFR, HER2, MUC1, phospho-mTOR, androgen/estrogens/progesterone receptors and Ki67 was carried out and evaluated in terms of progression-free and overall survival. High throughput molecular screening of key oncogenes was done in 107 patients using routine diagnostic methods and Sequenom technology.
Several therapy leads were identified, including high levels of HER2 and androgen receptors in salivary duct carcinomas, C-KIT in myoepithelial carcinomas and EGFR in mucoepidermoid carcinomas. Recurrent mutations involving downstream elements of the EGFR pathway were found in HRAS, notably in tumours with a myoepithelial component, and in other key oncogenes (KRAS/NRAS/PI3KCA/BRAF/MAP2K). On the other hand, < 1% of samples had EGFR or HER2 mutations.
Several tumour subtypes overexpressed targets of directed therapies suggesting potential therapy leads. Genotyping results suggest activation downstream of EGFR in 18 of the 107 samples that could be associated with low efficacy of EGFR inhibitors. Other molecules, such as PI3K/MEK or mTOR inhibitors, may have anti-tumour activity in this subgroup. The high mutation rate in HRAS highlights a novel key oncogenic event in MSGT.
|
Auteur(s) |
J. Cros
, Emilie Sbidian
1
, Stéphane Hans
2, 3
, H. Roussel
, Florient Scotté
4
, Eric Tartour
5
, Daniel Brasnu
3, 4
, Pierre Laurent-Puig
4
, P. Bruneval
6
, H. Blons
, Cécile Badoual
6, 7
1
LIC -
Laboratoire d'Investigation Clinique
( 206343 )
- Service de santé publique CHU Henri Mondor 94010 Créteil Cedex
- France
2
Service d'oto-rhino-laryngologie et chirurgie cervico-faciale [CHU HEGP]
( 25104 )
- Hôpital Européen Georges Pompidou
20, rue Leblanc 75908 Paris
- France
3
LPP -
LPP - Laboratoire de Phonétique et Phonologie - UMR 7018
( 986 )
- Université Sorbonne Nouvelle
Maison de la Recherche
4, rue des Irlandais
75005 PARIS
- France
4
HEGP -
Hôpital Européen Georges Pompidou [APHP]
( 300119 )
- 20, rue Leblanc, 75015 Paris
- France
5
U753 -
Cytokines et Immunologie des Tumeurs Humaines
( 2863 )
- Gustave Roussy. 114, rue Édouard-Vaillant 94805 Villejuif Cedex -France
- France
6
PARCC - UMR-S U970 -
Paris-Centre de Recherche Cardiovasculaire
( 81503 )
- 56 rue Leblanc
75015 PARIS
FRANCE
- France
7
Service d'anatomo-pathologie [CHU HEGP]
( 12949 )
- 20 Rue Leblanc, 75015 Paris
- France
|
Numéro |
10
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2013
|
Volume |
24
|
Page/Identifiant |
2624-2629
|
Domaine(s) |
|
Mots-clés |
en
C-KIT, EGFR, HER2, malignant salivary gland tumours, targeted therapies
|
DOI | 10.1093/annonc/mdt338 |
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