Test Catalog

Test Id : ENDCP

Hereditary Endocrine Cancer Panel, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Evaluation for 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
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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, WRN. For more information see Method Description, Targeted Genes and Methodology Details for Hereditary Endocrine Cancer Panel in Special Instructions.

 

Identification of a pathogenic variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for hereditary endocrine cancer syndromes.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Hereditary Endocrine Cancer Panel

Aliases
Lists additional common names for a test, as an aid in searching

Thyroid cancer

Endocrine cancer

Neuroendocrine tumor

Hereditary endocrine cancer

Hereditary paraganglioma-pheochromocytoma

Paraganglioma

PGL

Pheochromocytoma

PCC

Pituitary adenoma

Cowden syndrome

Neurofibromatosis type I

Multiple endocrine neoplasia type 1

MEN1

Multiple endocrine neoplasia type 2

MEN2

Hereditary paraganglioma-pheochromocytoma syndrome

Tuberous sclerosis complex

Von Hippel Lindau syndrome

Carney complex

NextGen sequencing test

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

Customization of this panel or single gene analysis for any gene present on this panel is 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 Mutation, Targeted Testing, Varies.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

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 specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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 in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Inherited Cancer Syndromes Patient Information (T519) in Special Instructions

3. Targeted Genes and Methodology Details for Hereditary Endocrine Cancer Panel in Special Instructions

4. If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

Useful For
Suggests clinical disorders or settings where the test may be helpful

Evaluation for 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
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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, WRN. For more information see Method Description, Targeted Genes and Methodology Details for Hereditary Endocrine Cancer Panel in Special Instructions.

 

Identification of a pathogenic variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for hereditary endocrine cancer syndromes.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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, no underlying genetic predisposition has yet been identified in most cases.(3-6)

 

Follicular and/or papillary thyroid cancers may be seen in families with PTEN hamartoma tumor syndrome (PHTS). Individuals with pathogenic 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 pathogenic DICER1 variants, as well as individuals with Carney complex, which is caused by pathogenic 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 pathogenic 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 pathogenic 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 commonly 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 pathogenic variants in FH increase risk for PGL/PCC.(14,15) Individuals with pathogenic 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
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

All detected variants are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(19) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.

 

To discuss the availability of further testing options or for assistance in the interpretation of these results, Mayo Clinic Laboratory genetic counselors can be contacted at 800-533-1710.

 

Technical Limitations
Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

 

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Insertions/deletions (indels) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller indels.

 

Deletion/Duplication Analysis

This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

 

This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

 

Genes may be added or removed based on updated clinical relevance. for the most up to date list of genes included in this test. For detailed information regarding gene specific performance and technical limitations see Method Description, Targeted Genes and Methodology Details for Hereditary Endocrine Cancer Panel in Special Instructions or contact a laboratory genetic counselor at 800-533-1710.

 

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

Reclassification of Variants
At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time.

 

Variant Evaluation

Evaluation and categorization of variants is performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline. Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgement.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

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 May 2021. Available at http://seer.cancer.gov/statfacts/html/thyro.html

3. Houlston RS, Stratton MR: Genetics of non-medullary thyroid cancer. QJM. 1995 Oct;88(10):685-693

4. Loh KC: Familial nonmedullary thyroid carcinoma: a meta-review of case series. Thyroid. 1997 Feb;7(1):107-113

5. Malchoff CD, Malchoff DM: Familial nonmedullary thyroid carcinoma. Semin Surg Oncol. 1999 Jan-Feb;16(1):16-18

6. Malchoff CD, Malchoff DM: The genetics of hereditary nonmedullary thyroid carcinoma. J Clin Endocrinol Metab. 2002 Jun;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 Dec;96(12):E2063-71

8. Stratakis CA, Raygada M: Carney complex. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated August 16, 2018. Accessed July 6, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1286/

9. Schultz KAP, Stewart DR, Kamihara J, et al: DICER1 tumor predisposition. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2014. Updated April 30, 2020. Accessed July 6, 2021. 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, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1999. Updated August 15, 2019. Accessed July 6, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1257/

12. Else T, Greenberg S, Fishbein L: Hereditary paraganglioma-pheochromocytoma syndromes. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2008, Updated October 4, 2018. Accessed July 6, 2021. 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 Sep 1;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 Jan;71:47-54

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 May 1;23(9):2440-2446

16. Kamihara J, Schultz KA, Rana HQ. FH Tumor predisposition syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2006. Updated August 13, 2020. Accessed July 6, 2021. 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 Jun;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 Dec;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 May;17(5):405-424

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known pathogenic variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for insertions/deletions (indels) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction (PCR)-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed. For details regarding the targeted genes analyzed for each test see Targeted Genes and Methodology Details for Hereditary Endocrine Cancer Panel in Special Instructions.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. For details regarding the specific gene regions not routinely covered see Targeted Genes and Methodology Details for Hereditary Endocrine Cancer Panel in Special Instructions.(Unpublished Mayo method)

 

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

 

Genes analyzed: 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, WRN

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

Supplemental

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 4 weeks

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81437

LOINC® Information

Test Id Test Order Name Order LOINC Value
ENDCP Hereditary Endocrine Cancer Panel In Process
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip
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 In Process
614714 Additional Information 48767-8
614715 Method 85069-3
614716 Genes Analyzed 48018-6
614717 Disclaimer 62364-5
614718 Released By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports