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.