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


CONCLUSIONS
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.
Glas
Annuska M
AM
Agendia BV, Slotervaart Medical Center 9D, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. annuska.glas@agendia.com
Floore
Arno
A
Delahaye
Leonie J M J
LJ
Witteveen
Anke T
AT
Pover
Rob C F
RC
Bakx
Niels
N
Lahti-Domenici
Jaana S T
JS
Bruinsma
Tako J
TJ
Warmoes
Marc O
MO
Bernards
René
R
Wessels
Lodewyk F A
LF
Van't Veer
Laura J
LJ
D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor