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J Clin Pathol. 2014 Nov;67(11):968-73. doi: 10.1136/jclinpath-2014-202514. Epub 2014 Jul 30.

Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies.

Author information

1
Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA Foundation Medicine, Inc., Cambridge, Massachusetts, USA.
2
Foundation Medicine, Inc., Cambridge, Massachusetts, USA.
3
Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA.

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.

KEYWORDS:

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

PMID:
25078331
PMCID:
PMC4215283
DOI:
10.1136/jclinpath-2014-202514
[Indexed for MEDLINE]
Free PMC Article
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