Characterization of adjacent breast tumors using oligonucleotide microarrays

Background: Current methodology often cannot distinguish second primary bre ast cancers from multifocal disease, a potentially important distinction fo r clinical management. In the present study we evaluated the use of oligonu cleotide-based microarray analysis in determining the clonality of tumors b y comparing gene expression profiles. Method: Total RNA was extracted from two tumors with no apparent physical c onnection that were located in the right breast of an 87-year-old woman dia gnosed with invasive ductal carcinoma (IDC). The RNA was hybridized to the Affymetrix Human Genome U95A Gene Chip(R) (12,500 known human genes) and an alyzed using the Gene Chip Analysis Suite(R) 3.3 (Affymetrix, Inc, Santa Cl ara, CA, USA) and JMPIN(R) 3.2.6 (SAS Institute, Inc, Cary, NC, USA). Gene expression profiles of tumors from five additional patients were compared i n order to evaluate the heterogeneity in gene expression between tumors wit h similar clinical characteristics. Results: The adjacent breast tumors had a pairwise correlation coefficient of 0.987, and were essentially indistinguishable by microarray analysis. An alysis of gene expression profiles from different individuals, however, gen erated a pairwise correlation coefficient of 0.710. Conclusion: Transcriptional profiling may be a useful diagnostic tool for d etermining tumor clonality and heterogeneity, and may ultimately impact on therapeutic decision making.