Metasignatures Identify Two Major Subtypes of Breast Cancer

Genome‐wide expression data from tumors and cell lines in breast cancer, together with drug response of cell lines, open prospects for integrative analyses that can lead to better personalized therapy. Drug responses and expression data collected from cell lines and tumors were used to generate trip...

Full description

Saved in:
Bibliographic Details
Published in:CPT: pharmacometrics and systems pharmacology 2013-03, Vol.2 (3), p.1-10
Main Authors: Duan, Q, Kou, Y, Clark, NR, Gordonov, S, Ma'ayan, A
Format: Article
Language:English
Subjects:
Biomarkers
Breast cancer
Cancer therapies
Drugs
Experiments
Gene expression
Genomes
Original
Patients
Principal components analysis
Studies
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Genome‐wide expression data from tumors and cell lines in breast cancer, together with drug response of cell lines, open prospects for integrative analyses that can lead to better personalized therapy. Drug responses and expression data collected from cell lines and tumors were used to generate tripartite networks connecting clusters of patients to cell lines and cell lines to drugs, to connect drugs to patients. Various approaches were applied to connect cell lines to tumor clusters: a standard method that uses a biomarker gene set, and new methods that compute metasignatures for transcription factors and histone modifications given upregulated genes in cell lines or tumors. The results from the metasignature analysis identify two major clusters of patients: one enriched for active histone marks and one for repressive marks. The tumors enriched for activation marks are correlated with poor prognosis. Overall, the analyses suggest new patient clustering, discover dysregulated pathways, and recommend individualized use of drugs to treat subsets of patients. CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e35; doi:10.1038/psp.2013.11; advance online publication 27 March 2013
ISSN:2163-8306
2163-8306
DOI:10.1038/psp.2013.11