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

Glas, Annuska M; Floore, Arno; Delahaye, Leonie JMJ; Witteveen, Anke T; Pover, Rob CF; Bakx, Niels; Lahti-Domenici, Jaana ST; Bruinsma, Tako J; Warmoes, Marc O; Bernards, Rene; Wessels, Lodewyk FA; Van 't Veer, Laura J
January 2006
BMC Genomics;2006, Vol. 7, p278
Academic Journal
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.


Related Articles

  • Gene expression levels assessed by oligonucleotide microarray analysis and quantitative real-time RT-PCR -- how well do they correlate? Dallas, Peter B; Gottardo, Nicholas G; Firth, Martin J; Beesley, Alex H; Hoffmann, Katrin; Terry, Philippa A; Freitas, Joseph R; Boag, Joanne M; Cummings, Aaron J; Kees, Ursula R // BMC Genomics;2005, Vol. 6, p59 

    Background: The use of microarray technology to assess gene expression levels is now widespread in biology. The validation of microarray results using independent mRNA quantitation techniques remains a desirable element of any microarray experiment. To facilitate the comparison of microarray...

  • Gene expression profile and response to trastuzumab–docetaxel-based treatment in breast carcinoma. Végran, F.; Boidot, R.; Coudert, B.; Fumoleau, P.; Arnould, L.; Garnier, J.; Causeret, S.; Fraise, J.; Dembélé, D.; Lizard-Nacol, S. // British Journal of Cancer;10/20/2009, Vol. 101 Issue 8, p1357 

    Background:Resistance to trastuzumab is often observed in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been shown to involve multiple potential mechanisms. We examined the ability of microarray analyses to determine the potential markers of...

  • The Utility of cDNA Microarrays. Clark, Charles T. // Genomics & Proteomics;Jan/Feb2003, Vol. 3 Issue 1, p35 

    Focuses on the increasing use of complementary DNA microarrays in gene expression analysis. Amount of RNA expressed by a gene; Components of complementary DNA microarrays; Advantages of oligonucleotide arrays over complementary DNA arrays.

  • Improving prediction accuracy of tumor classification by reusing genes discarded during gene selection. Yang, Jack Y.; Guo-Zheng Li; Hao-Hua Meng; Qu Yang, Mary; Youping Deng // BMC Genomics;2008 Supplement 1, Vol. 9, Special section p1 

    Background: Since the high dimensionality of gene expression microarray data sets degrades the generalization performance of classifiers, feature selection, which selects relevant features and discards irrelevant and redundant features, has been widely used in the bioinformatics field. Multitask...

  • Analysis of large-scale gene expression data. Sherlock, Gavin // Briefings in Bioinformatics;Dec2001, Vol. 2 Issue 4, p38 

    DNA microarray technology has resulted in the generation of large complex data sets, such that the bottleneck in biological investigation has shifted from data generation, to data analysis. This review discusses some of the algorithms and tools for the analysis and organisation of microarray...

  • Microarray results: how accurate are they? Kothapalli, Ravi; Yoder, Sean J.; Mane, Shrikant; Loughran Jr., Thomas P. // BMC Bioinformatics;2002, Vol. 3, p1 

    Background: DNA microarray technology is a powerful technique that was recently developed in order to analyze thousands of genes in a short time. Presently, microarrays, or chips, of the cDNA type and oligonucleotide type are available from several sources. The number of publications in this...

  • Three microarray platforms: an analysis of their concordance in profiling gene expression. Petersen, David; Chandramouli, GVR; Geoghegan, Joel; Hilburn, Joanne; Paarlberg, Jonathon; Chang Hee Kim; Munroe, David; Gangi, Lisa; Han, Jing; Puri, Raj; Staudt, Lou; Weinstein, John; Barrett, J Carl; Green, Jeffrey; Kawasaki, Ernest S // BMC Genomics;2005, Vol. 6, p63 

    Background: Microarrays for the analysis of gene expression are of three different types: short oligonucleotide (25-30 base), long oligonucleotide (50-80 base), and cDNA (highly variable in length). The short oligonucleotide and cDNA arrays have been the mainstay of expression analysis to date,...

  • Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays. Auer, Herbert; Newsom, David L; Nowak, Norma J; McHugh, Kirk M; Singh, Sunita; Chack-Yung Yu; Yan Yang; Wenger, Gail D; Gastier-Foster, Julie M; Kornacker, Karl // BMC Genomics;2007, Vol. 8, p111 

    Background: Array-based comparative genomic hybridization (aCGH) is a high-throughput method for measuring genome-wide DNA copy number changes. Current aCGH methods have limited resolution, sensitivity and reproducibility. Microarrays for aCGH are available only for a few organisms and...

  • Transcriptional signature of an adult brain tumor in Drosophila. Loop, Thomas; Leemans, Ronny; Stiefel, Urs; Hermida, Leandro; Egger, Boris; Fukang Xie; Primig, Michael; Certa, Ulrich; Fischbach, Friedrich; Reichert, Heinrich; Hirth, Frank // BMC Genomics;2004, Vol. 5, p1 

    Background: Mutations and gene expression alterations in brain tumors have been extensively investigated, however the causes of brain tumorigenesis are largely unknown. Animal models are necessary to correlate altered transcriptional activity and tumor phenotype and to better understand how...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics