Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Clin Cancer Res
; 21(7): 1688-98, 2015 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-25208879
ABSTRACT
PURPOSE:
Genomic profiling studies suggest that triple-negative breast cancer (TNBC) is a heterogeneous disease. In this study, we sought to define TNBC subtypes and identify subtype-specific markers and targets. EXPERIMENTALDESIGN:
RNA and DNA profiling analyses were conducted on 198 TNBC tumors [estrogen receptor (ER) negativity defined as Allred scale value ≤ 2] with >50% cellularity (discovery set n = 84; validation set n = 114) collected at Baylor College of Medicine (Houston, TX). An external dataset of seven publically accessible TNBC studies was used to confirm results. DNA copy number, disease-free survival (DFS), and disease-specific survival (DSS) were analyzed independently using these datasets.RESULTS:
We identified and confirmed four distinct TNBC subtypes (i) luminal androgen receptor (AR; LAR), (ii) mesenchymal (MES), (iii) basal-like immunosuppressed (BLIS), and (iv) basal-like immune-activated (BLIA). Of these, prognosis is worst for BLIS tumors and best for BLIA tumors for both DFS (log-rank test P = 0.042 and 0.041, respectively) and DSS (log-rank test P = 0.039 and 0.029, respectively). DNA copy number analysis produced two major groups (LAR and MES/BLIS/BLIA) and suggested that gene amplification drives gene expression in some cases [FGFR2 (BLIS)]. Putative subtype-specific targets were identified (i) LAR androgen receptor and the cell surface mucin MUC1, (ii) MES growth factor receptors [platelet-derived growth factor (PDGF) receptor A; c-Kit], (iii) BLIS an immunosuppressing molecule (VTCN1), and (iv) BLIA Stat signal transduction molecules and cytokines.CONCLUSION:
There are four stable TNBC subtypes characterized by the expression of distinct molecular profiles that have distinct prognoses. These studies identify novel subtype-specific targets that can be targeted in the future for the effective treatment of TNBCs.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transcriptoma
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Neoplasias de la Mama Triple Negativas
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Año:
2015
Tipo del documento:
Article