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Título

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

Autor Maliszewska, Agnieszka; Borrego, Salud ; Robledo, Mercedes
Fecha de publicación feb-2013
EditorAmerican Society for Investigative Pathology
Citación American Journal of Pathology 182(2): 350–362 (2013)
ResumenMedullary thyroid carcinoma accounts for 2% to 5% of thyroid malignancies, of which 75% are sporadic and the remaining 25% are hereditary and related to multiple endocrine neoplasia type 2 syndrome. Despite a genotype-phenotype correlation with specific germline RET mutations, knowledge of pathways specifically associated with each mutation and with non-RET-mutated sporadic MTC remains lacking. Gene expression patterns have provided a tool for identifying molecular events related to specific tumor types and to different clinical features that could help identify novel therapeutic targets. Using transcriptional profiling of 49 frozen MTC specimens classified as RET mutation, we identified PROM1, LOXL2, GFRA1, and DKK4 as related to RETM918T and GAL as related to RET634 mutation. An independent series of 19 frozen and 23 formalin-fixed, paraffin-embedded (FFPE) MTCs was used for validation by RT-qPCR. Two tissue microarrays containing 69 MTCs were available for IHC assays. According to pathway enrichment analysis and gene ontology biological processes, genes associated with the MTCM918T group were involved mainly in proliferative, cell adhesion, and general malignant metastatic effects and with Wnt, Notch, NFκB, JAK/Stat, and MAPK signaling pathways. Assays based on silencing of PROM1 by siRNAs performed in the MZ-CRC-1 cell line, harboring RETM918T, caused an increase in apoptotic nuclei, suggesting that PROM1 is necessary for survival of these cells. This is the first report of PROM1 overexpression among primary tumors.
Descripción Maliszewska, Agnieszka et al.
Versión del editorhttp://doi.org/10.1016/j.ajpath.2012.10.025
URI http://hdl.handle.net/10261/143512
DOI10.1016/j.ajpath.2012.10.025
Identificadoresissn: 0002-9440
e-issn: 1525-2191
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