RT Journal Article
SR Electronic
T1 Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 968
OP 973
DO 10.1136/jclinpath-2014-202514
VO 67
IS 11
A1 Ross, J S
A1 Wang, K
A1 Rand, J V
A1 Gay, L
A1 Presta, M J
A1 Sheehan, C E
A1 Ali, S M
A1 Elvin, J A
A1 Labrecque, E
A1 Hiemstra, C
A1 Buell, J
A1 Otto, G A
A1 Yelensky, R
A1 Lipson, D
A1 Morosini, D
A1 Chmielecki, J
A1 Miller, V A
A1 Stephens, P J
YR 2014
UL http://jcp.bmj.com/content/67/11/968.abstract
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.