摘要:
Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine neoplasias of neural crest origin that can be part of several inherited syndromes. Although their mRNA profiles are known to depend on genetic background, a number of questions related totumor biology and clinical behavior remain unanswered. As microRNAs (miRNAs) are key players in the modulation of gene expression, their comprehensive analysis could resolve some of these issues. Through characterization of miRNA profiles in 69 frozen tumors with germline mutations in the genes SDHD, SDHB, VHL, RET, NF1, TMEM127, and MAX, weidentified miRNA signatures specific to, as well as common among, the genetic groups of PCCs/PGLs. miRNA expression profiles were validated in an independent series of 30composed of VHL-, SDHB-, SDHD-, and RET-related formalin-fixed paraffin-embeddedPCC/PGL samples using quantitative real-time PCR. Upregulation of miR-210 in VHL- andSDHB-related PCCs/PGLs was verified, while miR-137 and miR-382 were confirmed asgenerally upregulated in PCCs/PGLs (except in MAX-related tumors). Also, we confirmedoverexpression of miR-133b as VHL-specific miRNAs, miR-488 and miR-885-5p as RET-specific miRNAs, and miR-183 and miR-96 as SDHB-specific miRNAs. To determine the potential roles miRNAs play in PCC/PGL pathogenesis, we performed bioinformatic integration andpathway analysis using matched mRNA profiling data that indicated a common enrichment
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