It was Rio Frio who in 2011 identified five different heterozygous DICER1 gene mutations in five families presenting autosomal dominant MNG with or without Sertoli–Leydig cell tumours. None of those pioneer studies highlighted the occurrence of thyroid lesions in that setting. Based on the presence of a variety of childhood tumours (PPB, cystic nephroma, Sertoli–Leydig cell tumours, embryonal rhabdomyosarcoma, among others), the authors proposed the term “DICER1 pleiotropic tumours predisposition syndrome” for this entity.
Fs chami font free download series#
found DICER1 mutations in 25 individuals of 19 families, within a series of 823 unrelated patients with a broad range of tumours. in 2009 with a case involving pleuropulmonary blastoma (PPB).
The evidence that DICER1 germline mutations represent a lead to distinctive and varied neoplasms was first reported by Hill et al. Only later was it verified that it shares the same locus as DICER1 in the chromosome 14 (14q32). During the study of a large Canadian family in 1986, with 18 cases of nontoxic multinodular goiter (MNG), a locus on chromosome 14q was identified and designated as ”‘multinodular goiter-1” (MNG1). 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.ĭICER1 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. On the other hand, in a DICER1 somatic mutation context, malignant tumours are more common. Within the syndromic context MNG is typically the most observed lesion.
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. 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. 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.
0 kommentar(er)
