Next-generation sequencing of 29 adrenocortical carcinoma samples identified at least one genomic alteration in 76% of cases, with 59% having targets for available therapies or clinical trials.
Observational (n=29)
Does next-generation sequencing identify potential therapeutic targets in adrenocortical carcinoma?
Next-generation sequencing of adrenocortical carcinoma identifies actionable genomic alterations in over half of cases, suggesting new targeted therapy options.
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.
Ross et al. (Wed,) conducted a observational in Adrenocortical carcinoma (n=29). Next-generation sequencing was evaluated on Presence of at least one genomic alteration. Next-generation sequencing of 29 adrenocortical carcinoma samples identified at least one genomic alteration in 76% of cases, with 59% having targets for available therapies or clinical trials.