Abstract
DICER1 protein is a member of the ribonuclease (RNAse) III family with a key role in the biogenesis of microRNAs (miRNA) and in microRNA processing, potentially affecting gene regulation at the post-transcriptional level. The role of DICER1 and its relevance to thyroid cellular processes and tumorigenesis have only recently been explored, following the acknowledgement that DICER1 germline and somatic changes can contribute not only to non-toxic multinodule goiter (MNG) lesions detected in individuals of affected families but also to a series of childhood tumours, including thyroid neoplasms, which can be identified from early infancy up until the decade of 40s. In a context of DICER1 germline gene mutation, thyroid lesions have recently been given importance, and they may represent either an index event within a syndromic context or the isolated event that may trigger a deeper and broader genomic analysis screening of individuals and their relatives, thereby preventing the consequences of a late diagnosis of malignancy. Within the syndromic context MNG is typically the most observed lesion. On the other hand, in a DICER1 somatic mutation context, malignant tumours are more common. In this review we describe the role of DICER protein, the genomic events that affect the DICER1 gene and their link to tumorigenesis as well as the frequency and pattern of benign and malignant thyroid lesions and the regulation of DICER1 within the thyroidal environment.
Highlights
DICER1 protein is a member of the ribonuclease (RNAse) III family, which has a key role in the biogenesis of microRNAs, potentially affecting gene regulation at the post-transcriptional level
The evidence that DICER1 germline mutations represent a lead to distinctive and varied neoplasms was first reported by Hill et al in 2009 [3] with a case involving pleuropulmonary blastoma (PPB)
Taking this fact into consideration, and the evidence of more recent studies demonstrating that DICER1 mutations are not restricted to benign thyroid lesions and may contribute biologically to more aggressive thyroid tumours (Table 1), the molecular testing for DICER1 could be recommended to patients whose thyroid lesions are diagnosed before the age of 40, when typically one would not expect to see genetic alterations in the most common thyroid cancer-related genes as often and where an individualized treatment and follow-up approach is required the most
Summary
DICER1 protein is a member of the ribonuclease (RNAse) III family, which has a key role in the biogenesis of microRNAs (miRNA), potentially affecting gene regulation at the post-transcriptional level. Chong et al found that, not absent in DICER1 mutated lesions—as shown by our group [2]—changes in other genes that are related with thyroid tumorigenesis (RAS, BRAF, RET, TSHR, EIF1AX and TP53, among others) are less common in lesions that present DICER1 hotspot mutations [28] Taking this fact into consideration, and the evidence of more recent studies demonstrating that DICER1 mutations are not restricted to benign thyroid lesions and may contribute biologically to more aggressive thyroid tumours (Table 1), the molecular testing for DICER1 could be recommended to patients whose thyroid lesions are diagnosed before the age of 40, when typically one would not expect to see genetic alterations in the most common thyroid cancer-related genes as often and where an individualized treatment and follow-up approach is required the most. ND, Not done. (a) Age at surgery. (b) Germline or somatic origin unknown. (c) The case is the same case of the studies [30,35]. (d) These two cases are the same cases of the study [30]. (e) The case is the same case of the study [36]
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