General information
The SALSA MLPA
Probemix P482 DICER1 is a
research use only (RUO) assay for the detection of deletions or duplications in the
DICER1 gene, which is associated with DICER1 syndrome.
DICER1 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). DICER1 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.
DICER1 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, deletions of the entire
DICER1 locus and in- or out-of-frame intragenic
DICER1 deletions have also been identified (for review see De Kock et al. 2019).
Multinodular goiter-1 (MNG1) with or without Sertoli-Leydig cell tumours (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 tumours, 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/ and González et al. 2022.
This SALSA MLPA probemix is not CE/FDA registered for use in diagnostic procedures. Purchase of this product includes a limited license for research purposes.
Probemix content
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 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 and online (
www.mrcholland.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.mrcholland.com.