Amplification of different satellite-DNAs in prostate cancer
Nurul Aida Ariffen, Antônio Augusto Ornellas, Gilda Alves, Ahmad Moay Shana'ah, Samiha Sharma, Stefanie Kankel, Elena Jamali, Bernhard Theis, Thomas Liehr
Abstract
In various solid tumors and corresponding cell lines, prior research has identified acquired copy number variations (CNVs) encompassing centromeric satellite-DNA sequences. This observation emerged from the application of centromeric probes (satellite-DNA) as controls in molecular cytogenetic investigations and diagnostics, although these accounts were largely anecdotal. In this study, we conducted a systematic screening for satellite-DNA sequence amplification in 31 prostate cancer (PCa) samples, a prevalent malignancy in men characterized by discernible molecular cytogenetic aberrations. Notably, PCa-typical genetic aberrations, such as TMPRSS2-ERG gene rearrangements and PTEN deletion, were identified in 12 and 6 out of the 31 PCa samples, respectively. Overall, PCa exhibited genomic instability marked by chromosomal gain or loss of signals across nearly all tested satellite-DNA regions, with particular emphasis on the Y-chromosome (18/31 cases). Remarkably, 5/12 PCa samples representing more advanced metastatic cancer displayed amplification of one or two satellite DNA stretches each, being detectable as blocks analogous to homogenously staining regions. Notably, these stretches included α-satellite DNA derived from chromosomes 2, 3, 4, 15, and 20, as well as satellite-III DNAs (D1Z1 and DYZ1). These findings align with recent discoveries indicating that α-satellite DNAs are expressed as long-non-coding RNAs in advanced cancer, particularly in the context of PCa.