Cytogenetic Equivalents of Satellite DNA Amplification are Detectable in Advanced Breast Cancers and Seem to Lead to Satellite RNA Expression

The cytogenetic equivalents of oncogene amplification are well-known in cancer cells as homogeneously staining regions (HSR) or double minutes (DM). We previously described similar amplifications of satellite-DNA (Sat-DNA) in advanced prostate cancer. In this study, we systematically screened for Sat-DNA amplification in 47 breast cancer (BCa) samples, which is a prevalent malignancy in women. Interphase fluorescence in situ hybridization (iFISH) was applied using 23 Sat-DNA probes and a probe for ErbB2/Her2 gene amplification. ErbB2/Her2 gene amplification was identified in 20 of the studied BCA samples; 13 showed an HSR pattern and seven showed a DM pattern by iFISH. Additionally, the application of 23 Sat-DNA probes revealed massive chromosome instability (CIN) in all samples studied. Notably, 15 out of 47 BCa samples displayed amplification of one or two Sat-DNAs. Each was detectable as HSR-like structures in 13 out of 15 cases. In two cases, Sat-DNA was amplified as DMs. Sat-III-DNA (1q12/HSat3 and D9Z3) was involved in nine cases, and α-Sat-DNA derived from chromosomes 9, 11, 17 and 18 showed amplification in nine cases. Sat-DNA amplification was positively aligned with advance in tumor grade, Ki67 concentration and positive ErbB2/Her2 immunohistochemistry status and/or gene amplification. Four selected cases with α-Sat-DNA amplification showed enhanced α-Sat-RNA-expression between 1.4- and 9.7-fold, while two cases without α-Sat-DNA amplification showed such RNA-presence only at very low levels. Overall, Sat-DNA amplification may be an overlooked feature of advanced solid tumors, as demonstrated here for BCa and in previous studies for prostate cancer and liposarcoma.