Molecular screening for a personalized treatment approach in advanced adrenocortical cancer

Maria Cristina De Martino, Abir Al Ghuzlan, Sebastien Aubert, Guillaume Assié, Jean Yves Scoazec, Sophie Leboulleux, Christine Do Cao, Rossella Libè, Cécile Nozières, Marc Lombès, François Pattou, Francoise Borson-Chazot, Ségolène Hescot, Clement Mazoyer, Jacques Young, Isabelle Borget, Annamaria Colao, Rosario Pivonello, Jean Charles Soria, Jerome BertheratMartin Schlumberger, Ludovic Lacroix, Eric Baudin

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    68 Citations (Scopus)

    Résumé

    Context: Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and scant treatment options. In ACC, no personalized approach has emerged but no extensive molecular screening has been performed to date. Objective: The objective of the study was toevaluate the presence of a large number of potentially targetable molecular events in a large cohort of advanced ACC. Design, Setting, and Participants: Weused hotspot gene sequencing (Ion Torrent, 40 patients) and comparative genomic hybridization (CGH; 28 patients; a subset of the entire cohort) in adult stage III-IV ACC samples to screen for mutations and copy number abnormalities of potential interest for therapeutic use in 46 and 130 genes, respectively. Results: At least one copy number alteration or mutation was found in 19 patients (47.5%). The most frequent mutations were detected on TP53, ATM, and CTNNB1 [6 of 40 (15%), 5 of 40 (12.5%), and 4 of 40 (10%), respectively]. The most frequent copy number alterations identified were: amplification of the CDK4 oncogene (5 of 28; 17.9%) and deletion of the CDKN2A (4 of 28; 14.3%) and CDKN2B (3 of 28; 10.7%) tumor suppressor genes. Amplifications of FGFR1, FGF9, or FRS2 were discovered in three subjects (10.7%). Associated alterations were: deletions of CDKN2A, CDKN2B with ATM mutations, and TP53 mutations with CTNNB1 mutations. Conclusions: No simple targetable molecular event emerged. Drugs targeting thecellcyclecould be the most relevant new therapeutic approach for patients with advanced ACC. Inhibitors of the fibroblast growth factor receptor pathway could also be a therapeutic option in a subset of patients, whereas other targeted therapies should be considered on a case-by-case basis.

    langue originaleAnglais
    Pages (de - à)4080-4088
    Nombre de pages9
    journalJournal of Clinical Endocrinology and Metabolism
    Volume98
    Numéro de publication10
    Les DOIs
    étatPublié - 1 oct. 2013

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