TY - JOUR
T1 - Molecular screening for a personalized treatment approach in advanced adrenocortical cancer
AU - De Martino, Maria Cristina
AU - Al Ghuzlan, Abir
AU - Aubert, Sebastien
AU - Assié, Guillaume
AU - Scoazec, Jean Yves
AU - Leboulleux, Sophie
AU - Do Cao, Christine
AU - Libè, Rossella
AU - Nozières, Cécile
AU - Lombès, Marc
AU - Pattou, François
AU - Borson-Chazot, Francoise
AU - Hescot, Ségolène
AU - Mazoyer, Clement
AU - Young, Jacques
AU - Borget, Isabelle
AU - Colao, Annamaria
AU - Pivonello, Rosario
AU - Soria, Jean Charles
AU - Bertherat, Jerome
AU - Schlumberger, Martin
AU - Lacroix, Ludovic
AU - Baudin, Eric
PY - 2013/10/1
Y1 - 2013/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84885227380&partnerID=8YFLogxK
U2 - 10.1210/jc.2013-2165
DO - 10.1210/jc.2013-2165
M3 - Article
C2 - 23979958
AN - SCOPUS:84885227380
SN - 0021-972X
VL - 98
SP - 4080
EP - 4088
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 10
ER -