Résumé

SY4-003

Progrès dans l'individualisation des cibles moléculaires potentiellement ciblables du corticosurrnélome stade III-IV

MC. De Martino*^a (Dr), L. Ludovic^b (Dr), S. Aubert^c (Dr), R. Libe^d (Dr), A. Al Ghuzlan^b (Dr), C. De La Fouchardiere^e (Dr), S. Hescot^f (Dr), G. Guillaume^g (Dr), A. Honoré^b (Dr), F. Deschamps^b (Dr), M. Lombès^f (Dr), F. Borson-Chazot^h (Dr), F. Pattou^c (Dr), J. Youngⁱ (Dr), I. Borget^b (Dr), M. Schlumberger^b (Pr), S. Leboulleux^b (Dr), JY. Scoazec^b (Pr), J. Bertherat^g (Pr), C. Do Cao^c (Dr), E. Baudin^b (Dr)

^a Gustave Roussy, Villejuif, FRANCE and Dipartimento di Madicina Clinica e Chirurgia, Naples, ITALIE ; ^b Gustave Roussy, Villejuif, FRANCE ; ^c CHRU, Lille, FRANCE ; ^d French Adrenal Cancer Network, Institut National du Cancer, Paris, FRANCE ; ^e Centre Léon Bérard, Lyon, FRANCE ; ^f Inserm U693, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, FRANCE ; ^g Institut Cochin, Paris, FRANCE ; ^h Hospices Civils de Lyon, Lyon, FRANCE ; ⁱ Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, FRANCE

* demartino.mc@gmail.com

Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and scant treatment options.

Purpose: 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.

Experimental design: We started by using 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. Thereafter whole exome sequencing was performed in 10 ACC samples to identified the recurrent variants in other genes not explored by hot spot gene sequencing . The presence and the frequency of most interesting variants emerged by previous approaches together with the results of the literature, including the recent exome study (Assié et al. 2014), were confirmed using target gene sequencing (Ion Torrent) in a validation cohort of 68 advanced ACC samples.

Results and Conclusion: No simple targetable molecular event emerged. Based on DNA alteration analyses performed in the largest series of advanced ACC , Wnt and cell cycle pathway alterations represent critical targets for future therapeutic development.

Future directions: The role Wnt and cell cycle pathway alterations as prognostic factors and as potential target for treatment in advanced ACC warrant further preclinical and clinical investigation.

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