Almost half of the human genome and as much as 40% of the mouse genome is composed of repetitive DNA sequences. The majority of these repeats are retrotransposons of the SINE and LINE families, and such repeats are generally repressed by epigenetic mechanisms. It has been proposed that these elements can act as methylation centers from which DNA methylation spreads into gene promoters in cancer. Contradictory to a methylation center function, we have found that retrotransposons are enriched near promoter CpG islands that stay methylation-free in cancer. Clearly, it is important to determine which influence, if any, these repetitive elements have on nearby gene promoters. Using an in vitro system, we confirm here that SINE B1 elements can influence the activity of downstream gene promoters, with acquisition of DNA methylation and loss of activating histone marks, thus resulting in a repressed state. SINE sequences themselves did not immediately acquire DNA methylation, but were marked by H3K9me2 and H3K27me3. Moreover, our bisulfite sequencing data did not support that gain of DNA methylation in gene promoters occurred by methylation spreading from SINE B1 repeats. Genome-wide analysis of SINE repeats distribution showed that their enrichment is directly correlated with the presence of USF1, USF2 and CTCF binding, proteins with insulator function. In summary, our work supports the concept that SINE repeats interfere negatively with gene expression and that their presence near gene promoters is counter-selected, except when the promoter is protected by an insulator element.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) derived from precursors of plasmacytoid dendritic cells is a very rare, unique, and highly aggressive immature hematopoietic malignancy, more frequently occurring among healthy elderly adults. BPDCN can be characterized by a striking predilection for cutaneous involvement, which is often detected incidentally by dermatologists and is difficult to clinically distinguish it from other primary skin lesions and histologically from leukemia/lymphoma cutis. Thus, histological diagnosis of cutaneous biopsies is crucial to correctly classify this entity. Most patients eventually progress to acute myeloid leukemia and are generally not curable. Here, we present 2 cases of classic BPDCN and discuss the origin of tumor and literature-based characteristic clinical and morphological features, evolving immunomarkers, and molecular genetic aspects of this neoplasm.
The eyelid can be the site of various malignant tumors, including epithelial, mesenchymal, lymphoproliferative, and endocrine neoplasms, all of which can present in unusual ways or mimic benign processes, often requiring biopsy for a definitive diagnosis. This review article presents a broad overview of some of the malignancies that have been reported to occur in eyelids, addressing clinical presentation and natural history, histologic and immunostaining characteristics, and genetic associations where relevant. The unique combination of functional importance, to protect and lubricate the eye, and cosmetic importance make management of eyelid lesions difficult. We describe a few of the diagnostic and treatment options that can be considered.
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