Converting a breast cancer microarray signature into a high-throughput diagnostic test

Annuska M Glas,Tako J Bruinsma,Leonie Jmj Delahaye,René Bernards,Jaana St Lahti-Domenici,Arno Floore,Marc O Warmoes,Anke T Witteveen,Laura J Van 'T Veer,Niels Bakx,Lodewyk Fa Wessels,Rob Cf Pover

doi:10.1186/1471-2164-7-278

Abstract

BackgroundA 70-gene tumor expression profile was established as a powerful predictor of disease outcome in young breast cancer patients. This profile, however, was generated on microarrays containing 25,000 60-mer oligonucleotides that are not designed for processing of many samples on a routine basis.ResultsTo facilitate its use in a diagnostic setting, the 70-gene prognosis profile was translated into a customized microarray (MammaPrint) containing a reduced set of 1,900 probes suitable for high throughput processing. RNA of 162 patient samples from two previous studies was subjected to hybridization to this custom array to validate the prognostic value. Classification results obtained from the original analysis were then compared to those generated using the algorithms based on the custom microarray and showed an extremely high correlation of prognosis prediction between the original data and those generated using the custom mini-array (p < 0.0001).ConclusionIn this report we demonstrate for the first time that microarray technology can be used as a reliable diagnostic tool. The data clearly demonstrate the reproducibility and robustness of the small custom-made microarray. The array is therefore an excellent tool to predict outcome of disease in breast cancer patients.

Highlights

A 70-gene tumor expression profile was established as a powerful predictor of disease outcome in young breast cancer patients
The Amsterdam 70-gene prognosis profile has been shown to outperform all clinical parameters in predicting distant metastasis [13]
In this paper we describe the development of a customized diagnostic breast cancer mini-array, MammaPrint, based on the Amsterdam 70-gene expression profile [6], and describe its reliable use in a diagnostic setting

Summary

Introduction

A 70-gene tumor expression profile was established as a powerful predictor of disease outcome in young breast cancer patients. This profile, was generated on microarrays containing 25,000 60-mer oligonucleotides that are not designed for processing of many samples on a routine basis. One study involved the discovery of a profile associated with the risk of early development of distant metastasis in young patients with lymph-node negative breast cancer [6]. The challenge is to predict the risk of metastasis at the time of primary diagnosis and accurately manage those patients identified as high-risk. The Amsterdam 70-gene prognosis profile has been shown to outperform all clinical parameters in predicting distant metastasis [13]. The ability to use this profile in a high throughput diagnostic setting would be a great advantage in the prognosis and treatment of breast cancer

Methods

Results

Discussion

Conclusion