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HelpTest ID: ENDCP Hereditary Endocrine Cancer Panel, Varies
Ordering Guidance
Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.
Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. For more information see FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated
Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. Molecular Genetics: Inherited Cancer Syndromes Patient Information (T519)
3. If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.
Useful For
Evaluating patients with a personal or family history suggestive of a hereditary endocrine tumor syndrome
Establishing a diagnosis of a hereditary endocrine tumor syndrome, allowing for targeted surveillance based on associated risks
Identifying genetic variants associated with increased risk for endocrine tumors, allowing for predictive testing and appropriate screening of at-risk family members
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 24 genes associated with hereditary endocrine cancer syndromes: AIP, APC (including promoters 1A and 1B), CDC73, CDKN1B, DICER1, FH, MAX, MEN1, NF1, PHOX2B, PRKAR1A, PTEN (including promoter), RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TP53, TSC1, TSC2, VHL, and WRN. For more information, see Method Description and Targeted Genes and Methodology Details for Hereditary Endocrine Cancer Panel.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for hereditary endocrine cancer syndromes.
Method Name
Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.
Reporting Name
Hereditary Endocrine Cancer PanelSpecimen Type
VariesSpecimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Clinical Information
Tumors occurring within the endocrine and neuroendocrine systems, including thyroid/parathyroid tumors, pituitary tumors, pheochromocytomas (PCC), and paragangliomas (PGL), may occasionally be caused by an underlying hereditary predisposition. Suspicion may be raised for a hereditary cause in families with a strong history of endocrine cancers, patients diagnosed with an endocrine cancer at an early age, patients with multiple primary endocrine cancer diagnoses, and patients with specific histological subtypes, such as medullary thyroid cancer.
The most common endocrine-related malignancy is thyroid cancer, with a lifetime risk of approximately 1.2%.(1,2) Papillary thyroid cancers are typically sporadic but can be seen in individuals or families with familial adenomatous polyposis (FAP) syndrome, caused by variants within the APC gene (cribriform-morular variant). Additionally, about 5% of cases of isolated papillary thyroid cancer cluster in a familial pattern; however, in most cases, no underlying genetic predisposition has yet been identified.(3-6)
Follicular and/or papillary thyroid cancers may be seen in families with PTEN hamartoma tumor syndrome (PHTS). Individuals with disease-causing PTEN variants have a 70-fold increased incidence of thyroid cancer compared to the general population.(7) Thyroid cancers with follicular or papillary features can also be seen in individuals with disease-causing DICER1 variants, as well as individuals with Carney complex, which is caused by disease-causing variants within the PRKAR1A gene.(8,9)
Approximately 25% of cases of medullary thyroid cancer (MTC) are caused by an inherited RET variant.(10) Some disease-causing RET variants are associated with only familial MTC, while others cause a syndrome called multiple endocrine neoplasia type 2 (MEN2). Individuals with MEN2 have a high risk for MTC and may also have other tumors of the endocrine/neuroendocrine system, including PGL, PCC, and parathyroid tumors.(11)
Parathyroid and pituitary tumors may be caused by disease-causing variants within MEN1, CDKN1B, and CDC73. The AIP gene is associated with hereditary predisposition for isolated pituitary adenomas.
PCC and PGL are rare neuroendocrine tumors, 30% of which may have an underlying hereditary predisposition.(12) The genes most frequently associated with increased risk for PGL/PCC are the succinate dehydrogenase-associated genes: SDHA, SDHAF2, SDHB, SDHC, and SDHD.
Germline alterations in the MAX gene are typically associated with increased risk for PCC, although some individuals have been identified with PGL. MAX variants occur in approximately 1% of patients with hereditary PGL/PCC syndromes.(13)
TMEM127 variants are most commonly associated with PCC and rarely PGL.(12) Alterations of TMEM127 account for approximately 2% of individuals with hereditary PGL/PCC (13).
Recent evidence suggests that disease-causing variants in FH increase risk for PGL/PCC.(14,15) Individuals with disease-causing FH variants also have a significantly increased risk for cutaneous or uterine leiomyomata and renal tumors.(16)
Alterations in VHL, NF1, and RET also increase risk for PGL/PCC in addition to other features and tumor types.(17)
The National Comprehensive Cancer Network and the American Cancer Society provide recommendations regarding the medical management of individuals with hereditary endocrine tumor syndromes.(17,18)
Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(19) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Clinical Reference
1. Geeta L, O'Dorisio T, McDougall R, Weigel RJ: Cancer of the endocrine system: Thyroid cancer. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG, eds. Abeloff's Clinical Oncology. 4th ed. Churchill Livingston; 2008
2. Surveillance Epidemiology and End Results Program: Cancer stat facts: Thyroid cancer. National Cancer Institute; 2018. Accessed April 26, 2024. Available at http://seer.cancer.gov/statfacts/html/thyro.html
3. Houlston RS, Stratton MR: Genetics of non-medullary thyroid cancer. QJM. 1995;88(10):685-693
4. Loh KC: Familial nonmedullary thyroid carcinoma: a meta-review of case series. Thyroid. 1997;7(1):107-113. doi:10.1089/thy.1997.7.107
5. Malchoff CD, Malchoff DM. Familial nonmedullary thyroid carcinoma. Semin Surg Oncol. 1999;16(1):16-18.
6. Malchoff CD, Malchoff DM. The genetics of hereditary nonmedullary thyroid carcinoma. J Clin Endocrinol Metab. 2002;87(6):2455-2459
7. Ngeow J, Mester J, Rybicki LA, Ni Y, Milas M, Eng C. Incidence and clinical characteristics of thyroid cancer in prospective series of individuals with Cowden and Cowden-like syndrome characterized by germline PTEN, SDH, or KLLN alterations. J Clin Endocrinol Metab. 2011;96(12):E2063-71
8. Stratakis CA, Raygada M: Carney complex. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated September 21, 2023. Accessed April 26, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1286/
9. Schultz KAP, Stewart DR, Kamihara J, et al. DICER1 tumor predisposition. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2014. Updated April 30, 2020. Accessed April 26, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK196157/
10. Shepet K, Alhefdhi A, Lai N, Mazeh H, Sippel R, Chen H: Hereditary medullary thyroid cancer: age-appropriate thyroidectomy improves disease-free survival. Ann Surg Oncol. 2013 May;20(5):1451-1455
11. Eng C: Multiple endocrine neoplasia type 2. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1999. Updated August 10, 2023. Accessed April 26, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1257/
12. Else T, Greenberg S, Fishbein L: Hereditary paraganglioma-pheochromocytoma syndromes. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2008, Updated September 21, 2023. Accessed April 26, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1548/
13. Bausch B, Schiavi F, Ni Y, et al: European-American-Asian Pheochromocytoma-Paraganglioma Registry Study Group. Clinical characterization of the pheochromocytoma and paraganglioma susceptibility genes SDHA, TMEM127, MAX, and SDHAF2 for gene-informed prevention. JAMA Oncol. 2017;3(9):1204-1212
14. Udager AM, Magers MJ, Goerke DM, et al. The utility of SDHB and FH immunohistochemistry in patients evaluated for hereditary paraganglioma-pheochromocytoma syndromes. Hum Pathol. 2018;71:47-54. doi:10.1016/j.humpath.2017
15. Castro-Vega LJ, Buffet A, De Cubas AA, et al. Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. Hum Mol Genet. 2014;23(9):2440-2446
16. Kamihara J, Schultz KA, Rana HQ. FH Tumor predisposition syndrome. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2006. Updated August 13, 2020. Accessed April 26, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1252/
17. Shah MH, Goldner WS, Halfdanarson TR, et al. NCCN Guidelines Insights: Neuroendocrine and adrenal tumors, version 2.2018. J Natl Compr Canc Netw. 2018;16(6):693-702
18. Haddad RI, Nasr C, Bischoff L, et al. NCCN Guidelines Insights: Thyroid carcinoma, version 2.2018. J Natl Compr Canc Netw. 2018;16(12):1429-1440
19. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424
Day(s) Performed
Varies
Report Available
14 to 21 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81437
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| ENDCP | Hereditary Endocrine Cancer Panel | In Process |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 614707 | Test Description | 62364-5 |
| 614708 | Specimen | 31208-2 |
| 614709 | Source | 31208-2 |
| 614710 | Result Summary | 50397-9 |
| 614711 | Result | 82939-0 |
| 614712 | Interpretation | 69047-9 |
| 614713 | Resources | 99622-3 |
| 614714 | Additional Information | 48767-8 |
| 614715 | Method | 85069-3 |
| 614716 | Genes Analyzed | 48018-6 |
| 614717 | Disclaimer | 62364-5 |
| 614718 | Released By | 18771-6 |
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