TY - JOUR T1 - Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies JF - Journal of Clinical Pathology JO - J Clin Pathol SP - 968 LP - 973 DO - 10.1136/jclinpath-2014-202514 VL - 67 IS - 11 AU - J S Ross AU - K Wang AU - J V Rand AU - L Gay AU - M J Presta AU - C E Sheehan AU - S M Ali AU - J A Elvin AU - E Labrecque AU - C Hiemstra AU - J Buell AU - G A Otto AU - R Yelensky AU - D Lipson AU - D Morosini AU - J Chmielecki AU - V A Miller AU - P J Stephens Y1 - 2014/11/01 UR - http://jcp.bmj.com/content/67/11/968.abstract N2 - Aims Adrenocortical carcinoma (ACC) carries a poor prognosis and current systemic cytotoxic therapies result in only modest improvement in overall survival. In this retrospective study, we performed a comprehensive genomic profiling of 29 consecutive ACC samples to identify potential targets of therapy not currently searched for in routine clinical practice. Methods DNA from 29 ACC was sequenced to high, uniform coverage (Illumina HiSeq) and analysed for genomic alterations (GAs). Results At least one GA was found in 22 (76%) ACC (mean 2.6 alterations per ACC). The most frequent GAs were in TP53 (34%), NF1 (14%), CDKN2A (14%), MEN1 (14%), CTNNB1 (10%) and ATM (10%). APC, CCND2, CDK4, DAXX, DNMT3A, KDM5C, LRP1B, MSH2 and RB1 were each altered in two cases (7%) and EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN and PTCH1 were each altered in a single case (3%). In 17 (59%) of ACC, at least one GA was associated with an available therapeutic or a mechanism-based clinical trial. Conclusions Next-generation sequencing can discover targets of therapy for relapsed and metastatic ACC and shows promise to improve outcomes for this aggressive form of cancer. ER -