title: Molecular screening for a personalized treatment approach in advanced adrenocortical cancer.
abstract: BACKGROUND
  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 to evaluate the presence of a large number of potentially targetable molecular events in a large cohort of advanced ACC.
  
  
  METHODS
  We used hot spot 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 the cell cycle could 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.
authors: PhD, Translational Research Laboratory and Biobank, Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif Cedex, France. ludovic.lacroix@igr.fr.
authors: Maria Cristina
authors: MC
authors: De Martino
authors: Abir
authors: A
authors: Al Ghuzlan
authors: Sebastien
authors: S
authors: Aubert
authors: Guillaume
authors: G
authors: Assié
authors: Jean-Yves
authors: JY
authors: Scoazec
authors: Sophie
authors: S
authors: Leboulleux
authors: Christine
authors: C
authors: Do Cao
authors: Rossella
authors: R
authors: Libè
authors: Cécile
authors: C
authors: Nozières
authors: Marc
authors: M
authors: Lombès
authors: François
authors: F
authors: Pattou
authors: Francoise
authors: F
authors: Borson-Chazot
authors: Ségolène
authors: S
authors: Hescot
authors: Clement
authors: C
authors: Mazoyer
authors: Jacques
authors: J
authors: Young
authors: Isabelle
authors: I
authors: Borget
authors: Annamaria
authors: A
authors: Colao
authors: Rosario
authors: R
authors: Pivonello
authors: Jean-Charles
authors: JC
authors: Soria
authors: Jerome
authors: J
authors: Bertherat
authors: Martin
authors: M
authors: Schlumberger
authors: Ludovic
authors: L
authors: Lacroix
authors: Eric
authors: E
authors: Baudin
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018268:Adrenocortical Carcinoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation