Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies.
J Clin Pathol
; 67(11): 968-73, 2014 Nov.
Article
en En
| MEDLINE
| ID: mdl-25078331
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Biomarcadores de Tumor
/
Neoplasias de la Corteza Suprarrenal
/
Carcinoma Corticosuprarrenal
/
Perfilación de la Expresión Génica
/
Terapia Molecular Dirigida
/
Secuenciación de Nucleótidos de Alto Rendimiento
/
Antineoplásicos
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Año:
2014
Tipo del documento:
Article