Genomic Alterations in Sporadic Synchronous Primary Breast Cancer Using Array and Metaphase Comparative Genomic Hybridization

Abstract

Synchronous primary breast cancer describes the occurrence of multiple tumors affecting one or both breasts at initial diagnosis. This provides a unique opportunity to identify tissue-specific genomic markers that characterize each tumor while controlling for the individual genetic background of a patient. The aim of this study was to examine the genomic alterations and degree of similarity between synchronous cancers. Using metaphase comparative genomic hybridization and array comparative genomic hybridization (aCGH), the genomic alterations of 23 synchronous breast cancers from 10 patients were examined at both chromosomal and gene levels. Synchronous breast cancers, when compared to their matched counterparts, were found to have a common core set of genetic alterations, with additional unique changes present in each. They also frequently exhibited features distinct from the more usual solitary primary breast cancers. The most frequent genomic alterations included chromosomal gains of 1q, 3p, 4q, and 8q, and losses of 11q, 12q, 16q, and 17p. aCGH identified copy number amplification in regions that are present in all 23 tumor samples, including 1p31.3–1p32.3 harboring JAK1. Our findings suggest that synchronous primary breast cancers represent a unique type of breast cancer and, at least in some instances, one tumor may give rise to the other.

Keywords

• Synchronous breast cancer
• microdissection
• comparative genomic hybridization (CGH)
• array CGH (aCGH)
• metaphase CGH (mCGH)