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Original article
Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies
  1. J S Ross1,2,
  2. K Wang2,
  3. J V Rand1,
  4. L Gay2,
  5. M J Presta1,
  6. C E Sheehan1,
  7. S M Ali2,
  8. J A Elvin2,
  9. E Labrecque2,
  10. C Hiemstra2,
  11. J Buell2,
  12. G A Otto2,
  13. R Yelensky2,
  14. D Lipson2,
  15. D Morosini2,
  16. J Chmielecki2,
  17. V A Miller2,
  18. P J Stephens2
  1. 1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA
  2. 2Foundation Medicine, Inc., Cambridge, Massachusetts, USA
  1. Correspondence to Dr Jeffrey S Ross, Department of Pathology, Albany Medical College, Mail Code 81, 47 New Scotland Avenue, Albany, NY 12208, USA; rossj{at}mail.amc.edu

Abstract

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.

  • Cancer Genetics
  • Endocrine Pathology
  • Molecular Pathology
  • Oncology
  • Gene Amplification

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/jclinpath-2014-202514

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