DICER1 somatic mutations strongly impair miRNA processing even in benign thyroid lesions
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Anello Marcello Poma1, Vincenzo Condello1, Maria Denaro1, Liborio Torregrossa2, Rossella Elisei3, Paolo Vitti3 and Fulvio Basolo1
1Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy
2Section of Pathology, University Hospital of Pisa, Pisa, Italy
3Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy
Fulvio Basolo, email: firstname.lastname@example.org
Keywords: thyroid cancer; DICER1; miRNA; mutation; follicular adenoma
Received: December 03, 2018 Accepted: January 16, 2019 Published: March 05, 2019
The alteration of miRNA processing is a driver event in several tumors including thyroid cancer. In particular, somatic DICER1 mutations, reported in follicular-patterned lesions, are shared by benign as well as malignant tumors. In the present study, we investigated the effects of alterations in the miRNA processing genes on the miRNA profile.
The study included 19 follicular adenomas (FAs) and 22 follicular variant of papillary thyroid carcinomas (FVPTCs). The mutational status in the hot spot regions of DICER1, DROSHA, TARBP2, DGCR8 and the most commonly affected genes in thyroid tumors was investigated on both tumor and paired normal tissues. The miRNA profile and the mRNA expression levels of DICER1, DROSHA, TARBP2, DGCR8 and XPO5 were also evaluated.
Two DICER1 RNase IIIb domain mutations were found in FAs. These lesions presented a considerable loss of 5p miRNAs. Fifteen miRNAs were specifically deregulated in DICER1-mutant lesions compared to FAs and FVPTCs. These miRNAs regulate crucial pathways in cancer such as Hippo, p53 and TGF-beta signalling.
DICER1 somatic mutations in the RNase IIIb domain are not specific for malignancy, but the miRNA imbalance that they cause is remarkable, especially with regard to the loss of 5p miRNAs. DICER1-mutant lesions have a characteristic miRNA deregulation, which is different from that of FVPTCs; nevertheless, this impairment is consistent with malignant transformation. Further studies providing the real risk of malignancy associated with DICER1 mutations and the evolution of DICER1-mutant lesions are needed to make them useful in the clinical practice.
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