PT  - JOURNAL ARTICLE
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
TI  - Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies
AID  - 10.1136/jclinpath-2014-202514
DP  - 2014 Nov 01
TA  - Journal of Clinical Pathology
PG  - 968--973
VI  - 67
IP  - 11
4099  - http://jcp.bmj.com/content/67/11/968.short
4100  - http://jcp.bmj.com/content/67/11/968.full
SO  - J Clin Pathol2014 Nov 01; 67
AB  - 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.