RESUMO
The pathogenesis of myotonic dystrophy type 2 includes the sequestration of MBNL proteins by expanded CCUG transcripts, which leads to an abnormal splicing of their target pre-mRNAs. We have found CCUG(exp) RNA transcripts of the ZNF9 gene associated with the formation of ribonuclear foci in human skeletal muscle and some non-muscle tissues present in muscle biopsies and skin excisions from myotonic dystrophy type 2 patients. Using RNA-FISH and immunofluorescence-FISH methods in combination with a high-resolution confocal microscopy, we demonstrate a different frequency of nuclei containing the CCUG(exp) foci, a different expression pattern of MBNL1 protein and a different sequestration of MBNL1 by CCUG(exp) repeats in skeletal muscle, vascular smooth muscle and endothelia, Schwann cells, adipocytes, and ectodermal derivatives. The level of CCUG(exp) transcription in epidermal and hair sheath cells is lower compared with that in other tissues examined. We suppose that non-muscle tissues of myotonic dystrophy type 2 patients might be affected by a similar molecular mechanism as the skeletal muscle, as suggested by our observation of an aberrant insulin receptor splicing in myotonic dystrophy type 2 adipocytes.
Assuntos
Músculo Esquelético/metabolismo , Transtornos Miotônicos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Actinas/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Análise de Variância , Antígenos CD34/metabolismo , Endotélio/metabolismo , Endotélio/patologia , Humanos , Microscopia Confocal , Transtornos Miotônicos/diagnóstico , Transtornos Miotônicos/genética , Transtornos Miotônicos/metabolismo , Transtornos Miotônicos/patologia , Distrofia Miotônica , Proteínas de Neurofilamentos/metabolismo , Transporte Proteico/fisiologia , RNA/metabolismo , Splicing de RNA/genética , Receptor de Insulina/genética , Sequências Repetitivas de Ácido Nucleico/genética , Proteínas S100/metabolismo , Pele/metabolismo , Pele/patologiaRESUMO
BACKGROUND AND AIM: The cytogenetic and diagnostic hallmark of mantle cell lymphoma (MCL) is translocation t(11;14)(q13;q32), resulting in overexpression of cyclin D1. Cyclin D1 expression was analysed in 32 cases of MCL. METHODS: The t(11;14) translocation was detected by fluorescence in situ hybridisation, level of cyclin D1 mRNA by competitive RT-PCR, and level of cyclin D1 and D2 proteins by immunohistochemistry and/or immunoblotting. RESULTS: In 30 cases, the presence of translocation t(11;14), a high level of cyclin D1 mRNA, and a high level of the cyclin D1 protein were confirmed. Two cyclin D1-negative cases overexpressing cyclin D2 were detected by immunoblotting. CONCLUSIONS: There are rare cyclin D1-negative cases of MCL overexpressing cyclin D2. Anti-cyclin D1 antibodies with low specificity can bind both cyclin D1 and cyclin D2, thus providing false cyclin D1-positive signals in immunohistochemical analysis.
