DESCRIPTION:

Genes were identified by expression clustering analysis of a large number of breast cancer samples. Direction of regulation was curated from supplemental table S3B. Values represent Bonferroni corrected p-values of T-tests shown in supplemental table S3C. p-value scores were selected to be <0.05. HGNC identifiers were mapped to gene symbols manually. Symbols were associated with HGNC identifiers that mapped to approved symbols if they mapped to more than one HGNC identifier. Symbols which were not confidently mapped were not included.

LABEL:

Up in MSL subtype of TNBC

SCORE TYPE:

P-Value

DATE ADDED:

2017-06-19

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA

TITLE:

Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.

JOURNAL:

The Journal of clinical investigation Jul 2011, Vol 121, pp. 2750-67

ABSTRACT:

Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and subtyping is necessary to better identify molecular-based therapies. In this study, we analyzed gene expression (GE) profiles from 21 breast cancer data sets and identified 587 TNBC cases. Cluster analysis identified 6 TNBC subtypes displaying unique GE and ontologies, including 2 basal-like (BL1 and BL2), an immunomodulatory (IM), a mesenchymal (M), a mesenchymal stem-like (MSL), and a luminal androgen receptor (LAR) subtype. Further, GE analysis allowed us to identify TNBC cell line models representative of these subtypes. Predicted &quot;driver&quot; signaling pathways were pharmacologically targeted in these cell line models as proof of concept that analysis of distinct GE signatures can inform therapy selection. BL1 and BL2 subtypes had higher expression of cell cycle and DNA damage response genes, and representative cell lines preferentially responded to cisplatin. M and MSL subtypes were enriched in GE for epithelial-mesenchymal transition, and growth factor pathways and cell models responded to NVP-BEZ235 (a PI3K/mTOR inhibitor) and dasatinib (an abl/src inhibitor). The LAR subtype includes patients with decreased relapse-free survival and was characterized by androgen receptor (AR) signaling. LAR cell lines were uniquely sensitive to bicalutamide (an AR antagonist). These data may be useful in biomarker selection, drug discovery, and clinical trial design that will enable alignment of TNBC patients to appropriate targeted therapies. PUBMED: 21633166
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