Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and scant treatment options.
Purpose: To look for new therapeutic approaches issued from the screening for common genetic variants in a large series of advanced ACC.
Experimental design: Whole exome sequencing have been performed in 10 advanced (stage III and IV) ACC samples to identify the recurrent variants. The presence and the frequency of most interesting variants on this series together with the results of the literature were confirmed using target gene sequencing (Ion Torrent) in a validation cohortof 68 advanced ACC samples\.
Results: Among the genes explored the most commonly altered gene was TP53 (35.5%) followed by CTNNB1 (22.1%); APC (19.1%); ZNRF3 (11.8%); RB1 (5.9%) and DAXX (5.9%); MED12 (2.9%); MEN1 (1.5%). Twenty percent of the evaluated samples presented a genetic variants in both Wnt and cell cycle pathways, while 33.8% did not have any genetic variants in the explored genes of these pathways.
Conclusion: 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.
18 - 21 May 2019
European Society of Endocrinology