Data from The Accumulation of Specific Amplifications Characterizes Two Different Genomic Pathways of Evolution of Familial Breast Tumors

Abstract

<div>Abstract<p><b>Purpose and Methods:</b> High-level DNA amplifications are recurrently found in breast cancer, and some of them are associated with poor patient prognosis. To determine their frequency and co-occurrence in familial breast cancer, we have analyzed 80 tumors previously characterized for <i>BRCA1</i> and <i>BRCA2</i> germ-line mutations (26 <i>BRCA1</i>, 18 <i>BRCA2</i>, and 36 non-<i>BRCA1/2</i>) using high-resolution comparative genomic hybridization.</p><p><b>Results:</b> Twenty-one regions were identified as recurrently amplified, such as 8q21-23 (26.25%), 17q22-25 (13.75%), 13q21-31 (12.50%), and 8q24 (11.25%), many of which were altered in each familial breast cancer group. These amplifications defined an amplifier phenotype that is correlated with a higher genomic instability. Based on these amplifications, two different genomic pathways have been established in association with 8q21-23 and/or 17q22-25 and with 13q21-31 amplification. These pathways are associated with specific genomic regions of amplification, carry specific immunohistochemical characteristics coincident with high and low aggressiveness, and have a trend to be associated with <i>BRCA1</i> and <i>BRCA2/X</i>, respectively.</p><p><b>Conclusion:</b> In summary, our data suggest the existence of two different patterns of evolution, probably common to familial and sporadic breast tumors.</p></div>