Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Intratumor Heterogeneity and Precision of Microarray-Based Predictors of Breast Cancer Biology and Clinical Outcome

ABSTRACT: Genome-wide expression profiling was performed on 50 core needle biopsies from 18 breast cancer patients using Affymetrix GeneChip Human Genome Plus 2.0 Arrays. Global profiles of expression were characterized using unsupervised clustering methods and variance components models. Precision of predictors of breast cancer biology and clinical outcome were evaluated by interclass correlation.

ORGANISM(S): Homo sapiens

SUBMITTER: Dawn Kernagis

PROVIDER: E-GEOD-23593 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Intratumor heterogeneity and precision of microarray-based predictors of breast cancer biology and clinical outcome.

Barry William T WT Kernagis Dawn N DN Dressman Holly K HK Griffis Ryan J RJ Hunter J'vonne D JD Olson John A JA Marks Jeff R JR Ginsburg Geoffrey S GS Marcom Paul K PK Nevins Joseph R JR Geradts Joseph J Datto Michael B MB

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20100405 13

<h4>Purpose</h4>Identifying sources of variation in expression microarray data and the effect of variance in gene expression measurements on complex predictive and diagnostic models is essential when translating microarray-based experimental approaches into clinical assays. The technical reproducibility of microarray platforms is well established. Here, we investigate the additional impact of intratumor heterogeneity, a largely unstudied component of variance, on the performance of several micro ...[more]

PMID: 20368555

Similar Datasets

Project description:PurposeIdentifying sources of variation in expression microarray data and the effect of variance in gene expression measurements on complex predictive and diagnostic models is essential when translating microarray-based experimental approaches into clinical assays. The technical reproducibility of microarray platforms is well established. Here, we investigate the additional impact of intratumor heterogeneity, a largely unstudied component of variance, on the performance of several microarray-based assays in breast cancer.Patients and methodsGenome-wide expression profiling was performed on 50 core needle biopsies from 18 breast cancer patients using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Global profiles of expression were characterized using unsupervised clustering methods and variance components models. Array-based measures of estrogen receptor (ER) and progesterone receptor (PR) status were compared with immunohistochemistry. The precision of genomic predictors of ER pathway status, recurrence risk, and sensitivity to chemotherapeutics was evaluated by interclass correlation.ResultsGlobal patterns of gene expression demonstrated that intratumor variation was substantially less than the total variation observed across the patient population. Nevertheless, a fraction of genes exhibited significant intratumor heterogeneity in expression. A high degree of reproducibility was observed in single-gene predictors of ER (intraclass correlation coefficient [ICC] = 0.94) and PR expression (ICC = 0.90), and in a multigene predictor of ER pathway activation (ICC = 0.98) with high concordance with immunohistochemistry. Substantial agreement was also observed for multigene signatures of cancer recurrence (ICC = 0.71) and chemotherapeutic sensitivity (ICC = 0.72 and 0.64).ConclusionIntratumor heterogeneity, although present at the level of individual gene expression, does not preclude precise microarray-based predictions of tumor behavior or clinical outcome in breast cancer patients.

Dataset Information

Intratumor Heterogeneity and Precision of Microarray-Based Predictors of Breast Cancer Biology and Clinical Outcome

Publications

Intratumor heterogeneity and precision of microarray-based predictors of breast cancer biology and clinical outcome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets