Methodology article

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

Annuska M Glas¹ , Arno Floore¹ , Leonie JMJ Delahaye¹ , Anke T Witteveen¹ , Rob CF Pover¹ , Niels Bakx¹ , Jaana ST Lahti-Domenici¹ , Tako J Bruinsma¹ , Marc O Warmoes¹ , René Bernards¹ , Lodewyk FA Wessels² and Laura J Van 't Veer¹

¹  Agendia BV, Slotervaart Medical Center 9D, Louwesweg 6, 1066 EC Amsterdam, The Netherlands

²  Netherlands Cancer Institute, department of Molecular Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

author email corresponding author email

BMC Genomics 2006, 7:278doi:10.1186/1471-2164-7-278

Published:	30 October 2006

Abstract

Background

A 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.

Results

To 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).

Conclusion

In 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.