Invitae DICER1 Syndrome Test


Test description

This test analyzes the DICER1 gene. Pathogenic variants in this gene are associated with DICER1 syndrome, also known as DICER1-pleuropulmonary blastoma familial tumor predisposition syndrome. This condition causes benign and malignant tumors in the lungs, kidneys, ovaries, and thyroid.

Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (1 gene)


Alternative tests to consider

DICER1 can also be ordered as part of a broader panel to test for different types of hereditary cancer conditions. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered for no additional charge.

DICER1 syndrome

DICER1 syndrome is an inherited disorder associated with an increased risk of both malignant and benign tumors that most often occur in the lungs, kidneys, ovaries, and thyroid. Tumors of the pituitary and pineal gland can also develop. However, it appears that many who carry a pathogenic variant never develop tumors.

Most of the associated tumors, including pleuropulmonary blastoma and cystic nephroma, present in childhood. Females can develop ovarian sex cord-stromal tumors, which include Sertoli-Leydig cell tumors, juvenile granulosa cell tumors, and gynandroblastoma. Adults with DICER1 syndrome may develop multinodular goiter, adenomas, and/or differentiated thyroid cancer.

Less frequently observed tumors associated with this condition include, ciliary body medulloepithelioma, botryoid-type embryonal rhabdomyosarcoma, nasal chondromesenchymal hamartoma, pituitary blastoma, and pineoblastoma.

Due to the rarity of DICER1 syndrome and the fact that some individuals with a pathogenic variant will never develop symptoms, the specific lifetime risk of developing DICER1-related tumors is unknown. Many of the tumors develop in childhood and most present before the age of 40. Ovarian sex cord-stromal tumors are limited to females and thyroid pathology typically presents in adulthood.

Sequencing analysis detects a pathogenic variant in DICER1 in 65% of affected individuals. While deletion/duplication analysis is also performed, the proportion of cases due to DICER1 copy number variants is currently not established.

Autosomal dominant. Most cases of DICER1 syndrome are inherited from a parent; approximately 20% occur as the result of a spontaneous de novo mutation.

The prevalence of DICER1 syndrome is currently unknown and appears to be rare. With the exception of thyroid pathology, tumors associated with this condition are very rare.

Analysis of the DICER1 gene may be considered in individuals with:

  • DICER1-associated tumors in childhood/early adulthood
  • biopsied tumor pathology and/or imaging findings consistent with DICER1 syndrome
  • a personal and/or family history of individuals with symptoms consistent with those of DICER1 syndrome

  1. Bahubeshi, A, et al. Germline DICER1 mutations and familial cystic nephroma. J. Med. Genet. 2010; 47(12):863-6. doi: 10.1136/jmg.2010.081216. PMID: 21036787
  2. Cao, WM, et al. Germline mutations of DICER1 in Chinese women with BRCA1/BRCA2-negative familial breast cancer. Genet. Mol. Res. 2014; 13(4):10754-60. doi: 10.4238/2014.December.18.16. PMID: 25526195
  3. Doros, L, et al. DICER1-Related Disorders. 2014 Apr 24. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 24761742
  4. Rio, Frio, T, et al. DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. JAMA. 2011; 305(1):68-77. doi: 10.1001/jama.2010.1910. PMID: 21205968
  5. 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. doi: 10.1136/jmg.2010.083790. PMID: 21266384
  6. Wu, Y, et al. DICER1 mutations in a patient with an ovarian Sertoli-Leydig tumor, well-differentiated fetal adenocarcinoma of the lung, and familial multinodular goiter. Eur J Med Genet. 2014; 57(11-12):621-5. doi: 10.1016/j.ejmg.2014.09.008. PMID: 25451712
  7. de, Kock, L, et al. Exploring the association Between DICER1 mutations and differentiated thyroid carcinoma. J. Clin. Endocrinol. Metab. 2014; 99(6):E1072-7. doi: 10.1210/jc.2013-4206. PMID: 24617712
  8. de, Kock, L, et al. Germ-line and somatic DICER1 mutations in pineoblastoma. Acta Neuropathol. 2014; 128(4):583-95. doi: 10.1007/s00401-014-1318-7. PMID: 25022261
  9. de, Kock, L, et al. Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. Acta Neuropathol. 2014; 128(1):111-22. doi: 10.1007/s00401-014-1285-z. PMID: 24839956

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
DICER1 NM_177438.2