1. Home
  2. Cancer genetics
  3. Adult
  4. Genetic testing for heritable pathogenic variants

DICER1 – genetic testing

On this page
Expand all Collapse all Back to top
  • Individual with one major or two minor indications for DICER1 testingr
  • Individual with a PPB-like sarcomar
  • Where a known DICER1 germline pathogenic variant is identified in a relative.*
  • Where a specific DICER1 pathogenic variant has been identified on somatic tumour testing.*

PPB = Pleuropulmonary blastoma 

* In these settings a variant-specific test (rather than sequencing a single gene or gene panel) may be more appropriate and cost effective. 

The decision to offer a genetic test should be based on the pre-test probability of identifying a heritable pathogenic variant, the performance of the test (e.g. false negative rate).

For individuals at risk of a known pathogenic variant, predictive genetic testing is recommended before 4 months of age so that pulmonary screening can be initiated in infancy.

The results of the following investigations may significantly influence the likelihood of detecting a heritable pathogenic variant in the DICER1 gene:

  • verification and/or review of relevant histopathology.r
  • verification and/or review of tumour classification based on DNA methylation profiling (e.g. DICER1-mutant class: primary intracranial sarcoma).
Factors Probability of detecting a heritable pathogenic variant

Individuals diagnosed with:

- Pleuropulmonary blastoma (PPB)

- Cystic nephroma

- Sertoli-Leydig cell tumour of the ovary

 

≥70%r

>70%r

>50%rr

Individuals with one or more of the following rare tumours:r

  • Embryonal rhabdomyosarcoma of the uterine cervix
  • Ciliary body medulloepithelioma
  • Nasal chondromesenchymal hamartoma
  • Pituitary blastoma
  • Pineoblastoma
  • Anaplastic sarcoma of the kidney
 May be >10%*

Individuals with two of these clinical features or one feature and a tumour associated with DICER1 syndrome:r

  • Juvenile granulosa cell tumour and gynandroblastoma
  • Multinodular thyroid disease in childhood
  • Differentiated thyroid cancer in childhood
  • Medulloblastoma
  • Juvenile hamartomatous intestinal polyps, especially terminal ileum
 May be >10%*
Familial Wilms tumour 1–5%r
Patient has a first or second degree relative with a documented DICER1 pathogenic variant Up to 50%*

*Pathogenic variant detection rate is high, but data on the frequency of DICER1 pathogenic variants in unselected, population-based series with regards to the other manifestations of DICER1 syndrome is limited. Data regarding the probability of detecting a heritable pathogenic variant is available from studies where patients have been ascertained on the basis of pathology and/or family history clinically suggestive of DICER1 syndrome (probands) and then cascade testing of at risk relatives (carriers).

Genetic testing is not indicated where there is a personal or family history of Wilms tumour with no other features of DICER1 syndrome (unless part of panel testing).

Predictive testing should never be ordered for a variant of uncertain significance or a benign/likely benign variant.

A range of testing methodologies are needed to identify pathogenic changes in the DICER1 gene including:

  • sequencing
  • copy number analysis.

Information about DNA tests and testing laboratories is available from: 

A variant-specific test (rather than sequencing a single gene or gene panel) may be more appropriate and cost effective where a relative is known to have a germline pathogenic variant or a pathogenic variant has been identified in the patient’s tumour. 

If a decision is made to test this gene as part of a cancer gene panel, care should be taken to select a panel where the individual genes tested have both clinical validity and clinical utility.

If this gene is tested using genomic sequencing (“next generation sequencing” or NGS), and testing has not identified a pathogenic variant, the value of testing using another methodology should be considered.

If genetic testing in DNA from peripheral blood does not identify a pathogenic variant, testing of other tumour and tissue samples may be indicated to assess for mosaicism.

Result Reference databases Considerations and advice
Pathogenic variant search
Pathogenic variant

ClinVar

UMD

LOVD

InSight
Variant of uncertain significance

Surveillance may still be required depending on the clinical and family history

Review pathogenicity of variants periodically

Additional tumour testing should be considered if other samples available

Identify other genes for which a pathogenic variant search could be considered 
No reportable variant  

Surveillance may still be required depending on the clinical and family history

Identify other genes for which a pathogenic variant search could be considered 
Predictive testing
Family pathogenic variant identified  
Family pathogenic variant not found   Screening based on a revised risk estimate

If a pathogenic variant is identified, refer to a clinical genetics service or familial cancer centre for review, family risk notification and predictive testing.

If a variant of uncertain significance is identified, consider referral to a clinical genetics service or familial cancer centre for review and guidance.

If a mosaic pathogenic variant is identified, refer to a clinical genetics service or familial cancer centre for review and guidance about the penetrance of phenotypic features (including cancer risk).

For additional information about the management of genetic test results when ordered by a non-genetic healthcare professional refer to eviQ’s Guide for health professionals ordering genetic testing.

[%id%]
[%title%]
[%abstract%]

Version 9

Date Summary of changes
19/01/2024

Protocol reviewed by paediatric cancer genetics reference committee at July 2023 meeting. Discussions continued via email and MS Teams. Approved for publication with the following changes made:

  • Target population: added "Individual with a PPB-like sarcoma"
  • Investigations before genetic testing: added "Verification and/or review of tumour classification based on DNA methylation profiling..."

Version increased to V.9. Approved on 11/01/2024, changes published on 19/01/2024. Review in 2 years.
17/09/2024 Review due date updated as per consensus of the eviQ cancer genetics chairs.

Version 8

Date Summary of changes
20/02/2023

The following sections of the document were updated to align with the new eviQ cancer genetics genetic testing template:

  • Target population: 
    • Added "Where a specific pathogenic variant has been identified on somatic tumour testing *"
    • Added "*In these settings a variant-specific test (rather than sequencing a single gene or gene panel) may be more appropriate and cost effective."
    • Removed "patient's choice" from "The decision to offer a genetic test should be based on the pre­-test probability of identifying a heritable pathogenic variant, the performance of the test (e.g. false negative rate), and the patient's choice."
  • Probability of a heritable pathogenic variant:
    • Removed "The frequency of heritable pathogenic variants in the DICER1 gene in unselected individuals with pleuropulmonary blastoma (PPB) is approximately 70%."
  • Circumstances in which testing is not indicated:
    •  Removed "A variant-specific test (rather than sequencing a single gene or gene panel) may be more cost effective and appropriate where: 
      • a known pathogenic variant has been identified in a relative
      • a specific pathogenic variant has been identified on somatic tumour testing."
  • Testing methods:
    • Added "A variant-specific test (rather than sequencing a single gene or gene panel) may be more appropriate and cost effective where a relative is known to have a germline pathogenic variant or a pathogenic variant has been identified in the patient’s tumour."
    • Removed "e.g. MLPA and Sanger sequencing"
  • Result interpretation:
    • HGMD and DMuDB removed from table.
    • Template sentence updated.

Version increased to V.8. 

Version 7

Date Summary of changes
22/12/2021

Protocol reviewed by paediatric cancer genetics reference committee at July 2021 meeting. Discussions continued via email and MS Teams. Approved for publication with the following changes made:

  • Target population: minor wording changes
  • Testing methods: removed link to 'European Directory of DNA Diagnostic Laboratories'
  • Result interpretation: 
    • Table row - Variant of uncertain significance - Considerations and advice: added 'Additional tumour testing should be considered if other samples available'
    • 'If a variant of uncertain significance is identified refer to a clinical genetics service or familial cancer centre for review and guidance.' added under the table.

Version increased to V.7. Approved on 22/12/2021, changes published on 13/01/2022. Review in 2 years.

Version 6

Date Summary of changes
09/12/2020

The following sections of the document were updated to align with the new eviQ cancer genetics genetic testing template:

  • Related pages: added link to "Guide for health professionals ordering genetic testing". Removed link to "Pre-test counselling"
  • Probability of a heritable pathogenic variant: last row of table - probability changed from "50% or 25%" to "Up to 50%"
  • Circumstances in which testing is not indicated: template wording updated
  • Testing methods: template wording updated
  • Result interpretation: table format updated. Reference databases added. Template sentence added (including link to "Guide for health professionals ordering genetic testing")
  • Counselling: section deleted
  • Website resources: section deleted.

Version number increased to V.6.

Version 5

Date Summary of changes
14/11/2019
  • Added link to DICER1 - risk management (child) protocol in the 'Related pages' and in the 'Result interpretation' section
  • "Mutation" changed to "pathogenic variant" and "unknown significance" changed to "uncertain significance" throughout document for consistency among eviQ cancer genetics protocols per agreement among the cancer genetics reference committees' chairs.
  • Definition of "pathogenic variant" added as a pop-up

Version number changed to V.5

Version 4

Date Summary of changes
25/10/2016

New protocol discussed at March 2016 cancer genetics reference committee meeting.

Approved and published on eviQ. Review two yearly.
31/05/2017 Transferred to new eviQ website. Version number changed to V.2.     
01/06/2018 'Gene Tests' link in Testing Methods section relabelled as GeneReviews.
03/07/2019

Protocol reviewed and presented at the November 2018 RCM. Discussion continued over email and document approved for publication with the following changes:

  • Target population:
    • ​First two bullet points removed. New bullet point added 'Indications for DICER1 testing' with link to new table.
    • Sentence removed: 'Testing is best done in the context of a research study.'
  • Probability of a heritable mutation:
    • 80% changed to 70% in initial sentence.
    • 'Most individuals will have personal or family history suggestive of familial PPB.' removed from above table. 
    • ​Changes made to table with newer references.
    • 'Familial Wilms tumour' added.
    • '25-50%' changed to '50% or 25%' for probability of a heritable mutation in patient has a first or second degree relative with a documented pathogenic mutation, as per template update.
  • Circumstances in which testing is not indicated:
    • '(unless part of panel testing)' added.
    • template changes applied.
  • Testing methods: Template sentences added.
  • Result interpretation: Template changes applied.
  • References: Updated.

Version changed to V.3. To undergo review in two years.
28/08/2019 Protocol title changed from 'Genetic testing for heritable mutations in the DICER1 gene' to 'DICER1 genetic testing' in accordance with Cancer Genetics Reference Committees' consensus. Version number increased to V.4.

The information contained in this document is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to care or treatment. Any clinician seeking to apply or consult this document is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

Send feedback for this page

First approved:
Last reviewed:
Review due:

The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/1724

06 Oct 2024