Dicer1 is a highly conserved RNaseIII endoribonuclease. It plays a critical role in the biogenesis of microRNAs (miRNAs), which are small regulatory RNAs responsible for post-transcriptional gene silencing, controlling over half of human protein-coding genes [3]. Dicer1 deficiency leads to miRNA dysregulation and changes in gene expression.

Pathogenic germline Dicer1 variants cause a hereditary cancer predisposition syndrome with diverse manifestations. These include increased risks for pleuropulmonary blastoma (PPB), ovarian sex-cord-stromal tumors (like Sertoli-Leydig cell tumor), as well as other tumors such as lung cysts, cystic nephroma, renal sarcoma, Wilms tumor, nodular hyperplasia of the thyroid, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, genitourinary embryonal rhabdomyosarcoma, and brain tumors (pineoblastoma and pituitary blastoma) [1]. In the female genital tract, germline Dicer1 mutations are associated with rare tumors like Sertoli-Leydig cell tumor, embryonal rhabdomyosarcoma of the cervix, gynandroblastoma, and juvenile granulosa cell tumor, and somatic mutations are found in others such as adenosarcoma [2].

In conclusion, Dicer1 is essential for miRNA biogenesis and post-transcriptional gene regulation. Research on Dicer1-associated syndromes, mainly through identification of germline and somatic mutations in various tumors, has revealed its significant role in the development of multiple cancers. Understanding Dicer1's function helps in developing strategies for early detection, surveillance, and treatment of Dicer1-associated neoplasms [1,2].

References:

1. Schultz, Kris Ann P, Williams, Gretchen M, Kamihara, Junne, Messinger, Yoav H, Hill, D Ashley. 2018. DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies. In Clinical cancer research : an official journal of the American Association for Cancer Research, 24, 2251-2261. doi:10.1158/1078-0432.CCR-17-3089. https://pubmed.ncbi.nlm.nih.gov/29343557/

2. Han, Lucy M, Weiel, Julianna J, Longacre, Teri A, Folkins, Ann K. 2022. DICER1-associated Tumors in the Female Genital Tract: Molecular Basis, Clinicopathologic Features, and Differential Diagnosis. In Advances in anatomic pathology, 29, 297-308. doi:10.1097/PAP.0000000000000351. https://pubmed.ncbi.nlm.nih.gov/35778792/

3. Thunders, Michelle, Delahunt, Brett. 2020. Gene of the month: DICER1: ruler and controller. In Journal of clinical pathology, 74, 69-72. doi:10.1136/jclinpath-2020-207203. https://pubmed.ncbi.nlm.nih.gov/33293352/