A REST derived gene signature stratifies glioblastomas into chemotherapy resistant and responsive disease.
BMC Genomics
; 13: 686, 2012 Dec 07.
Article
en En
| MEDLINE
| ID: mdl-23216891
ABSTRACT
BACKGROUND:
Glioblastomas are the most common central nervous system neoplasia in adults, with 9,000 cases in the US annually. Glioblastoma multiformae, the most aggressive glioma subtype, has an 18% one-year survival rate, and 3% two year survival rate. Recent work has highlighted the role of the transcription factor RE1 Silencing Transcription Factor, REST in glioblastoma but how REST function correlates with disease outcome has not been described.METHOD:
Using a bioinformatic approach and mining of publicly available microarray datasets, we describe an aggressive subtype of gliomas defined by a gene signature derived from REST. Using this REST gene signature we predict that REST function is enhanced in advanced glioblastoma. We compare disease outcomes between tumors based on REST status and treatment regimen, and describe downstream targets of REST that may contribute to the decreased benefits observed with high dose chemotherapy in REM tumors.RESULTS:
We present human data showing that patients with "REST Enhanced Malignancies" (REM) tumors present with a shorter disease free survival compared to non-REM gliomas. Importantly, REM tumors are refractory to multiple rounds of chemotherapy and patients fail to respond to this line of treatment.CONCLUSIONS:
This report is the first to describe a REST gene signature that predicts response to multiple rounds of chemotherapy, the mainline therapy for this disease. The REST gene signature may have important clinical implications for the treatment of glioblastoma.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Biomarcadores de Tumor
/
Glioblastoma
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
BMC Genomics
Asunto de la revista:
GENETICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos