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

Autor: J S Ross, K Wang, J V Rand, L Gay, M J Presta, C E Sheehan, S M Ali, J A Elvin, E Labrecque, C Hiemstra, J Buell, G A Otto, R Yelensky, D Lipson, D Morosini, J Chmielecki, V A Miller, P J Stephens
Rok vydání: 2014
Předmět:
Neuroblastoma RAS viral oncogene homolog
Oncology
Adult
Male
medicine.medical_specialty
Biopsy
PDGFRB
Antineoplastic Agents
Bioinformatics
medicine.disease_cause
Endocrine Pathology
Pathology and Forensic Medicine
Young Adult
Breast cancer
CDKN2A
Predictive Value of Tests
Internal medicine
medicine
Adrenocortical Carcinoma
Biomarkers
Tumor
Cancer Genetics
Adrenocortical carcinoma
Humans
Genetic Predisposition to Disease
Molecular Targeted Therapy
Precision Medicine
neoplasms
Aged
Retrospective Studies
Molecular pathology
business.industry
Gene Expression Profiling
Patient Selection
Gene Amplification
Cancer
High-Throughput Nucleotide Sequencing
General Medicine
Middle Aged
medicine.disease
Adrenal Cortex Neoplasms
Drug Design
Female
Original Article
KRAS
business
Molecular Pathology
Signal Transduction
Zdroj: Journal of Clinical Pathology
ISSN: 1472-4146
Popis: AimsAdrenocortical 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.MethodsDNA from 29 ACC was sequenced to high, uniform coverage (Illumina HiSeq) and analysed for genomic alterations (GAs).ResultsAt 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.ConclusionsNext-generation sequencing can discover targets of therapy for relapsed and metastatic ACC and shows promise to improve outcomes for this aggressive form of cancer.
Databáze: OpenAIRE
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