Differential Gene Expression of Medullary Thyroid Carcinoma Reveals Specific Markers Associated with Genetic Conditions

摘要: Medullary thyroid carcinoma accounts for 2% to 5% of malignancies, which 75% are sporadic and the remaining 25% hereditary related multiple endocrine neoplasia type 2 syndrome. Despite a genotype-phenotype correlation with specific germline RET mutations, knowledge pathways specifically associated each mutation non-RET-mutated MTC remains lacking. Gene expression patterns have provided tool identifying molecular events tumor types different clinical features that could help identify novel therapeutic targets. Using transcriptional profiling 49 frozen specimens classified as mutation, we identified PROM1, LOXL2, GFRA1, DKK4 RET(M918T) GAL RET(634) mutation. An independent series 19 23 formalin-fixed, paraffin-embedded (FFPE) MTCs was used validation by RT-qPCR. Two tissue microarrays containing 69 were available IHC assays. According pathway enrichment analysis gene ontology biological processes, genes MTC(M918T) group involved mainly in proliferative, cell adhesion, general malignant metastatic effects Wnt, Notch, NFκB, JAK/Stat, MAPK signaling pathways. Assays based on silencing PROM1 siRNAs performed MZ-CRC-1 line, harboring RET(M918T), caused an increase apoptotic nuclei, suggesting is necessary survival these cells. This first report overexpression among primary tumors.