Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany; Laboratory, Subang Jaya Medical Centre, Subang Jaya, Selangor, Malaysia.
Urology Service, Hospital Mário Kröeff, Rio de Janeiro, Brazil.
Pathol Res Pract. 2024 Apr;256:155269. doi: 10.1016/j.prp.2024.155269. Epub 2024 Mar 21.
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.
在各种实体瘤和相应的细胞系中，先前的研究已经确定了包含着着丝粒卫星 DNA 序列的获得性拷贝数变异 (CNVs)。这一观察结果来自于着丝粒探针 (卫星 DNA) 在分子细胞遗传学研究和诊断中的应用作为对照，尽管这些报道在很大程度上只是传闻。在这项研究中，我们对 31 个前列腺癌 (PCa) 样本进行了卫星 DNA 序列扩增的系统筛选，PCa 是一种常见的男性恶性肿瘤，具有明显的分子细胞遗传学异常。值得注意的是，在 31 个 PCa 样本中，分别有 12 个和 6 个出现了 PCa 典型的遗传异常，如 TMPRSS2-ERG 基因重排和 PTEN 缺失。总的来说，PCa 表现出基因组不稳定性，表现为几乎所有测试的卫星 DNA 区域的染色体增益或丢失信号，特别是在 Y 染色体上 (18/31 例)。值得注意的是，5/12 个代表更晚期转移性癌症的 PCa 样本每个都显示出一个或两个卫星 DNA 片段的扩增，可检测到类似于均匀染色区域的块。值得注意的是，这些片段包括来自染色体 2、3、4、15 和 20 的α-卫星 DNA，以及卫星 III DNA (D1Z1 和 DYZ1)。这些发现与最近的发现一致，表明α-卫星 DNA 在晚期癌症中作为长非编码 RNA 表达，特别是在 PCa 的情况下。
