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  • Test code: 01301
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Thyroid Cancer Panel

Test description

The Invitae Thyroid Cancer Panel analyzes up to 11 genes that are associated with an increased lifetime risk of developing thyroid cancer. These genes were selected based on the available evidence to date to provide Invitae’s most comprehensive hereditary thyroid cancer panel. Many of these genes are also associated with an increased risk of other types of cancer.

Genetic testing of these genes 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 (7 genes)

APC CHEK2 DICER1 PRKAR1A PTEN RET TP53

Add-on Preliminary-evidence Genes for Thyroid Cancer (4 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

MEN1 SDHB SDHD WRN

  • Carney complex
  • Cowden and Cowden-like syndrome
  • DICER1 syndrome
  • Familial adenomatous polyposis (FAP)
  • Li-Fraumeni syndrome (LFS)
  • Multiple endocrine neoplasia type 2 (MEN2)

Thyroid cancer occurs in approximately 1 of 170 individuals in the general population. Most cases of thyroid cancer are sporadic; however, approximately 5%–10% have a familial component and are due to an identifiable pathogenic variant. The most common type of thyroid cancer, accounting for more than 90% of all cases, is non-medullary thyroid cancer (NMTC). Approximately 3%–10% of NMTC cases have a familial component.

Medullary thyroid carcinoma (MTC) is a relatively uncommon type of thyroid malignancy. It is more strongly associated with hereditary cancer syndromes.The familial form of MTC accounts for 20%–25% of cases and is usually either familial MTC (FMTC) syndrome or a component of multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B).

Unlike sporadic cases, hereditary thyroid cancers are often characterized by earlier disease onset and may also be syndromic, with other multi-system features. The genes on this panel are associated with hereditary predisposition to developing thyroid cancer. Inclusion of these genes is expected to increase the clinical sensitivity of this test.

In individuals with a pathogenic variant in one of these genes, the risk of developing cancer is significantly higher. Identifying those at higher risk may allow for additional screening, surveillance, and interventions, which could result in risk-reduction and early diagnosis and increase the chances of successful treatment and survival.

Individuals with a pathogenic variant in one of these genes have an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develop cancer. Further, the same variant may manifest with different symptoms, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may be beneficial. For gene-associated cancer risks, see the table below.

GeneConditionThyroid cancer riskOther associated cancers/features
APC familial adenomatous polyposis up to 12% (PMID: 22425061) colon, duodenal, pancreatic, hepatic, central nervous system
CHEK2 CHEK2-related conditions elevated (PMID: 25583358, 15492928, 24599715) breast, colon, prostate, kidney
DICER1 DICER1 syndrome benign thyroid lesions—elevated thyroid cancer—unknown risk (PMID: 24617712, 21266384) pleuropulmonary blastoma, cystic nephroma, Sertoli-Leydig cell tumors, juvenile granulosa cell tumors, gynandroblastoma
PRKAR1A Carney complex thyroid adenoma or carcinoma and multiple thyroid nodules—elevated (PMID: 12203783, 16756677) myxomas, schwannomas, Sertoli cell tumors, skin pigmentary findings
PTEN Cowden syndrome 35% (PMID: 22252256) breast, uterine, kidney, skin findings
RET multiple endocrine neoplasia type 2 medullary thyroid cancer— >98% (PMID: 14561794, 17895320) pheochromocytoma, paragangliomas,
TP53 Li-Fraumeni syndrome elevated (PMID: 20522432) breast, sarcoma, leukemia, central nervous system, adrenocortical carcinoma, choroid plexus carcinoma

Elevated: There is evidence of association, but the penetrance and risk are not well characterized.
Unknown: Based on small studies, the risk is possibly increased, though not well-described.

The genes on this panel have autosomal dominant inheritance in association with thyroid cancer.

This panel may be considered for individuals who have a personal or family history of:

  • multiple family members with thyroid and/or other cancers
  • thyroid cancer before age 45
  • medullary thyroid cancer or pheochromocytoma
  • thyroid cancer and another type of cancer in the same individual

There are also some common, general features suggestive of a hereditary cancer syndrome family. These include:

  • cancer diagnosed at an unusually young age
  • different types of cancer that have occurred independently in the same person
  • cancer that has developed in both organs of a set of paired organs (e.g., both kidneys)
  • several close blood relatives that have the same type of cancer
  • unusual cases of a specific cancer type (e.g., breast cancer in a man)
  1. Tan, MH, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin. Cancer Res. 2012; 18(2):400-7. doi: 10.1158/1078-0432.CCR-11-2283. PMID: 22252256
  2. Eng, C. PTEN Hamartoma Tumor Syndrome (PHTS). 2001 Nov 29. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1488/ PMID: 20301661
  3. Marquard, J, Eng, C. Multiple Endocrine Neoplasia Type 2. 1999 Sep 27. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1257/ PMID: 20301434
  4. Doros, L, et al. DICER1-Related Disorders. 2014 Apr 24. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK196157/ PMID: 24761742
  5. Schneider, K, et al. Li-Fraumeni Syndrome. 1999 Jan 19. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle. PMID: 20301488
  6. 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
  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. Machens, A, Dralle, H. Genotype-phenotype based surgical concept of hereditary medullary thyroid carcinoma. World J Surg. 2007; 31(5):957-68. doi: 10.1007/s00268-006-0769-y. PMID: 17453286
  9. Brandi, ML, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J. Clin. Endocrinol. Metab. 2001; 86(12):5658-71. doi: 10.1210/jcem.86.12.8070. PMID: 11739416
  10. Ruijs, MW, et al. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J. Med. Genet. 2010; 47(6):421-8. PMID: 20522432
  11. Kirmani, S, Young, WF. Hereditary Paraganglioma-Pheochromocytoma Syndromes. 2008 May 21. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1548/ PMID: 20301715
  12. American, Thyroid, Association, Guidelines, Task, Force, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009; 19(6):565-612. doi: 10.1089/thy.2008.0403. PMID: 19469690
  13. Jasperson, KW, Burt, RW. APC-Associated Polyposis Conditions. 1998 Dec 18. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301519
  14. Stratakis, CA, et al. Carney Complex. 2003 Feb 05. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301463
  15. Cybulski, C, et al. CHEK2 is a multiorgan cancer susceptibility gene. Am. J. Hum. Genet. 2004; 75(6):1131-5. PMID: 15492928
  16. Steinhagen, E, et al. The prevalence of thyroid cancer and benign thyroid disease in patients with familial adenomatous polyposis may be higher than previously recognized. Clin Colorectal Cancer. 2012; 11(4):304-8. PMID: 22425061
  17. Siołek, M, et al. CHEK2 mutations and the risk of papillary thyroid cancer. Int. J. Cancer. 2015; :None. PMID: 25583358
  18. Wójcicka, A, et al. Variants in the ATM-CHEK2-BRCA1 axis determine genetic predisposition and clinical presentation of papillary thyroid carcinoma. Genes Chromosomes Cancer. 2014; 53(6):516-23. PMID: 24599715
  19. Sandrini, F, et al. Regulatory subunit type I-alpha of protein kinase A (PRKAR1A): a tumor-suppressor gene for sporadic thyroid cancer. Genes Chromosomes Cancer. 2002; 35(2):182-92. PMID: 12203783
  20. Bertherat, J. Carney complex (CNC). Orphanet J Rare Dis. 2006; 1:21. PMID: 16756677
  21. Machens, A, et al. Early malignant progression of hereditary medullary thyroid cancer. N. Engl. J. Med. 2003; 349(16):1517-25. PMID: 14561794
  22. Elisei, R, et al. RET genetic screening in patients with medullary thyroid cancer and their relatives: experience with 807 individuals at one center. J. Clin. Endocrinol. Metab. 2007; 92(12):4725-9. PMID: 17895320
  23. Bubien, V, et al. High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome. J. Med. Genet. 2013; 50(4):255-63. PMID: 23335809
  24. Riegert-Johnson, DL, et al. Cancer and Lhermitte-Duclos disease are common in Cowden syndrome patients. Hered Cancer Clin Pract. 2010; 8(1):6. PMID: 20565722
  25. Mester, J, Eng, C. Cowden syndrome: recognizing and managing a not-so-rare hereditary cancer syndrome. J Surg Oncol. 2015; 111(1):125-30. PMID: 25132236
  26. 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
  27. Moline, J, Eng, C. Multiple endocrine neoplasia type 2: an overview. Genet. Med. 2011; 13(9):755-64. PMID: 21552134
  28. Salehian, B, Samoa, R. RET gene abnormalities and thyroid disease: who should be screened and when. J Clin Res Pediatr Endocrinol. 2013; 5 Suppl 1:70-8. PMID: 23455356
  29. Eng, C, et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA. 1996; 276(19):1575-9. PMID: 8918855

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 in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
APC* NM_000038.5
CHEK2 NM_007194.3
DICER1 NM_177438.2
MEN1 NM_130799.2
PRKAR1A NM_002734.4
PTEN* NM_000314.4
RET NM_020975.4
SDHB NM_003000.2
SDHD NM_003002.3
TP53* NM_000546.5
WRN* NM_000553.4

APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis.
PTEN: Deletion/duplication analysis covers the promoter region.
TP53: Deletion/duplication analysis covers the promoter region.
WRN: Deletion/duplication analysis is not offered for exons 10 or 11.