A preliminary study of concurrent gains and losses across gene expression profiles and comparative genomic hybridization in Taiwanese breast cancer patients

Abstract

Purpose: The aim of the study was to perform genome-wide characterization of Taiwanese breast cancer at the molecular level by integrating 2 microarray technologies: comparative genomic hybridization (CGH) for analyzing DNA copy number changes, and gene expression profiles for determining transcriptional variations. Concurrent gains and losses from the same subject across genomic and transcriptional contexts may indicate potential biomarkers for endemic breast cancer. Methods: Fourteen pairs of cancerous and normal breast tissue were collected prospectively. Genomic DNA, messenger RNA, and corresponding normal controls were extracted from fresh frozen samples. Affymetrix® U133 plus 2.0 and Agilent® aCGH Human 105k microarrays were used for gene expression profiling and for detecting copy number variation. Concurrent gains and losses were declared if and only if significant changes in a coherent manner were observed for both gene expression and array CGH platforms within the same study subject. Results: Among the 14 breast cancer samples that were assayed, 7 were estrogen receptor (ER)-positive. The most common repeated concurrent gains (in 33% of the samples) were LAPTM4B, HRSP12, WISP1, SQLE, GINS4, LYZ , and DSCC1 . For clinical ER status relevance, there were 294 concurrent gains and 133 concurrent losses, and these were reduced to 30 and 27 cytobands, respectively. Concurrent gains were more common among ER-negative tumors in 1p32, 1p34, 1q21-23, and 17q25, whereas for ER-positive tumors, a gain in 8p11 was reported. Concurrent losses were observed in 8p21 for ER-positive breast cancers. Conclusions: Breast cancer oncogenesis could originate from DNA copy number changes and persist through transcription in gene expression patterns. Genes with coherent patterns at both chromosomal and transcriptional levels are more likely to serve as potential biomarkers for sporadic breast cancer. In the current study, we identified several candidate genes specific for Taiwanese breast cancer, and their clinical implications deserve extensive evaluation with more samples in the future.