ABSTRACT
We report a case of a 49-year-old male patient suffering from an intraspinal tumor in the lumbar vertebra. The neoplasm was composed of mono-morphic spindle cells, arrayed in a patternless pattern in a background of prominent myxoid hyaline stroma with perivascular collagen rings in hyper-cellular regions. Instead, aggregated collagen fibers arranged into nodules and apparent calcium deposition were found in hypo-cellular regions. The tumor cells showed immunopositivity with S100 and CD34, whereas lacked SOX10 expression, which were reminiscent of a group of S100 and CD34 co-expression soft tissue spindle cell lesions having recurrent fusions including RAF1, BRAF, NTRK1/2/3, and RET genes. Interestingly, a novel anaplastic lymphoma kinase (ALK)- echinoderm microtubule-associated protein-like 4 (EML4) gene fusion was revealed. To our best knowledge, it was the first time to identify such gene fusion in the Orientals among this mentioned group, and it expands the molecular genetic spectrum of this specific group. The clinical relevance of this novel fusion requires further investigations.
ABSTRACT
Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.