Pleuropulmonary Blastoma (PPB) Family Tumor and Dysplasia Syndrome, DICER1 Syndrome

DICER1 mutations are implicated in a broad range of tumors: pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian Sertoli-Leydig cell tumors (SLCTs), ciliary body medulloepithelioma (CBME) and other tumor types.

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DICER1 mutations are implicated in a broad range of tumors: pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian Sertoli-Leydig cell tumors (SLCTs), ciliary body medulloepithelioma (CBME) and other tumor types.

Germline DICER1 haploinsufficiency predisposes to a broad range of tumors, most significantly pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian Sertoli-Leydig cell tumors (SLCTs), ciliary body medulloepithelioma (CBME), as well as various other tumor types. Collectively, this condition is called DICER1 syndrome, also previously known as "PPB family tumor and dysplasia syndrome." DICER1 mutations are inherited in an autosomal dominant fashion with incomplete penetrance and variable expressivity.

The Ambry Test: Pleuropulmonary Blastoma-DICER1 detects mutations in the DICER1 gene by full gene sequence analysis of all coding domains and splice junctions. Identification of a DICER1 mutation can aid diagnosis and may dramatically improve outcome, particularly for pleuropulmonary blastoma (PPB), which can show significant clinical overlap with other types of lung cysts. DICER1 molecular testing is indicated in patients who are clinically suspected to have PPB, cystic nephroma, and ovarian Sertoli-Leydig tumors. 

Disease Name 
Pleuropulmonary Blastoma (PPB) Family Tumor and Dysplasia syndrome
DICER1 Syndrome
Disease Information 

The DICER1 gene encodes a dsRNA-specific ribonuclease (RNase) III endonuclease, which is required by the RNA interference (RNAi) pathway to produce the active small RNA component that represses gene expression. Germline DICER1 haploinsufficiency predisposes to a broad range of tumors, most significantly pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian Sertoli-Leydig cell tumors (SLCTs), ciliary body medulloepithelioma (CBME), as well as various other tumor types. Collectively, this condition is called DICER1 syndrome, also previously known as "PPB family tumor and dysplasia syndrome." DICER1 mutations are inherited in an autosomal dominant fashion with incomplete penetrance and variable expressivity. Heterozygous mutations of DICER1, with retention of the wild-type allele, have also been detected in a wide variety of cancer cells.1.2,3

Mutation of the DICER1 gene is found in approximately 50-70% of patients with PPB,1 and the prevalence of mutations in the other conditions may be considerable. Identification of a DICER1 mutation can aid diagnosis and management, particularly for PPB, which can show significant clinical overlap with other types of lung cysts.4 The range of different tumors that can occur in individuals with DICER1 mutations is broad, and it is likely that more associated tumors will be identified as further genetic testing is performed. 

Testing Benefits & Indication 

Identification of a DICER1 mutation can aid diagnosis and may dramatically improve outcome, particularly for pleuropulmonary blastoma (PPB), which can show significant clinical overlap with other types of lung cysts. DICER1 molecular testing is indicated in patients who are clinically suspected to have PPB, cystic nephroma, and ovarian Sertoli-Leydig tumors. DICER1 testing may also be considered for differential diagnosis, carrier testing for individuals with a family history, and for at risk pregnancies.

Test Description 

This Ambry test detects mutations in the DICER1 gene by full gene sequence analysis of all coding domains and splice junctions. Specific mutation analysis for individual DICER1 mutations known to be in the family is also available. 

Mutation Detection Rate 

This Ambry test identifies >99% of described mutations (analytic sensitivity). Approximately 50-75% of patients with pleuropulmonary blastoma (PPB) have a detectable mutation in the DICER1 gene sequence (clinical sensitivity).

Specimen Requirements 

 

Blood: Collect 3 – 5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Saliva: Collect 2 ml into OrageneTM DNA Self-Collection container. Store and ship at room temperature.
DNA: Minimum DNA Amount of 5μg of DNA at a concentration of ~100ng/μl in 50μl TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 20μg. Store frozen and ship on ice or dry ice.  

 

Turnaround Time 

 

TECHNIQUE DAYS
DICER1 Gene Sequencing Analysis 10-21

 

Specialty 
Genes 
References 

1. Slade I et al. DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet. 2011;48(4):273 – 8. [PMID: 21266384]

2. Hill DA et al. DICER1 mutations in familial pleuropulmonary blastoma. Science. 2009;325(5943):965. [PMID: 19556464]

3. Bahubeshi A et al. Germline DICER1 mutations and familial cystic nephroma. J Med Genet. 2010;47(12):863 – 6. [PMID: 21036787]

4. Priest JR et al. Pulmonary cysts in early childhood and the risk of malignancy. Pediatr Pulmonol. 2009;44(1):14 – 30. [PMID: 19061226]