The SALSA MLPA
Probemix P482 DICER1 is a research use only (RUO)
assay for the detection of deletions or duplications in the DICER1
which is associated with DICER1 syndrome.
gene locates on 14q32.13 (hg18), consists of 27 exons and encodes cytoplasmic endoribonuclease (RNase) III enzyme. DICER1 has a central role in the RNA interference pathway, as it cleaves double-stranded RNA molecules into small RNAs including microRNA (miRNA) and small interfering RNA (siRNA). DICER facilitates the incorporation of these RNAs into Argonoute protein, forming the RNA-induced silencing complex (RISC). The activated RISC recognizes a specific mRNA target sequence and can either guide degradation or inhibit translation of the molecule.
syndrome or DICER1
-related pleuropulmonary blastoma cancer predisposition syndrome (OMIM 601200), is a rare pleiotropic tumour predisposition syndrome manifesting usually in children or young adults and it is characterised by benign and malignant tumours in lungs, ovaries, thyroid gland, kidneys and brain (pineal and pituitary glands). DICER1
syndrome is inherited in an autosomal dominant pattern, but may also arise de novo
in the germline or in a somatic mosaic manner. It is estimated that 80% of the germline pathogenic variants are inherited from a parent and 20% are de novo
(see GeneReviews https://www.ncbi.nlm.nih.gov/books/NBK196157/
). Most of the described mutations in DICER1
are loss-of-function point or frameshift mutations, however, also deletions of the entire DICER1
locus and in- or out-of-frame intragenic DICER1
deletions have been also described (for review see De Kock et al. 2019).
Multinodular goiter-1 (MNG1) with or without Sertoli-Leydig cell tumors (OMIM 138800) is also caused by heterozygous mutations in the DICER1
gene. Unlike DICER1
syndrome, MNG1 is a common disorder characterized by nodular enlargement of the thyroid gland and some individuals may also develop Sertoli-Leydig cell tumors, usually of the ovary.
Additionally, mutations in DICER1
are recurrent in diverse set of cancers e.g. in sporadic pleuropulmonary blastoma, gonadal-, Wilms’ and endometrial tumours and anaplastic sarcomas of the kidney. Although miRNAs are required for normal cell fitness, selective inactivation of DICER1
, especially mutations in the RNase IIIb domain affecting the metal ion-binding residues, can benefit cancer cells (Vedanayagam et al. 2019).
More information is available at https://www.ncbi.nlm.nih.gov/books/NBK196157/
The SALSA MLPA Probemix P482-A1 DICER1 contains 50 MLPA probes with amplification products between 124 and 500 nucleotides (nt). This includes 31 probes for the DICER1
gene, and four probes centromeric and three probes telomeric to DICER1
gene. In addition, 12 reference probes are included that detect target relatively copy number stable regions in various cancer types. Complete probe sequences and the identity of the genes detected by the reference probes are available in Table 2b and online (www.mlpa.com
This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity fragments (Q-fragments), two DNA Denaturation fragments (D-fragments), one Benchmark fragment, and one chromosome X and one chromosome Y-specific fragment. More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at www.mlpa.com