• 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




Associated disorders

The MEN1 gene is associated with autosomal dominant multiple endocrine neoplasia type 1 (MEN1) syndrome (MedGen UID: 9957) and familial isolated hyperparathyroidism (FIHP) (OMIM: 145000).

The gene MEN1 encodes the menin protein, a putative tumor suppressor. Menin has been shown to localize to the nucleus and inhibit transcriptional activation by transcription factor JunD, but the function of this protein is largely unknown.

Multiple endocrine neoplasia type 1
MedGen UID: 9957

Clinical Condition
Multiple endocrine neoplasia type 1 (MEN1) syndrome is characterized by varying combinations of parathyroid, pancreatic neuroendocrine, and anterior pituitary tumors, with 94% penetrance by age 50. Some individuals may also develop carcinoid tumors, adrenocortical tumors, meningiomas, facial angiofibromas, collagenomas, and lipomas (PMID: 23565397, 11739416, 22723327, 26363542). Endocrine tumors become symptomatic due to hormone overproduction or by growth of the tumor itself (PMID: 20301710). Parathyroid tumors are the main MEN1-associated endocrinopathy, occurring in >95% of affected individuals (PMID: 22723327, 11739416). Primary hyperparathyroidism is usually the presenting symptom with the typical age of onset between 20 and 25 years of age (PMID: 26363542).

MEN1 syndrome is caused by mutations in the MEN1 gene. Pathogenic MEN1 variants have also been identified in individuals with familial isolated hyperparathyroidism (FIHP), which is characterized by parathyroid adenoma or hyperplasia without other associated endocrinopathies (PMID: 11454510, 12213668, 12699448).

Gene Information
The MEN1 gene is a tumor suppressor gene that encodes the protein menin. Menin is a component of a histone methyltransferase complex, which methylates histone H3, suggesting that it functions as a transcriptional regulator. Menin also interacts with a large number of proteins that play a role in the inhibition of cell proliferation, genomic stability, and cell cycle control. The exact function of menin and the mechanism by which alterations in menin lead to endocrine tumors are still unclear (PMID: 26363542; UniProtKB – PO00255 [MEN1_HUMAN], http://www.uniprot.org/uniprot/O00255. Accessed August 2017; Genetics Home Reference. MEN1 gene. https://ghr.nlm.nih.gov/gene/MEN1. Accessed August 2017).

MEN1 syndrome has autosomal dominant inheritance. This means that an individual with a pathogenic variant has a 50% chance of passing the condition on to their offspring. Once a pathogenic mutation is detected in an individual, it is possible to identify at-risk relatives who can pursue testing for this specific familial variant. Most cases are inherited from a parent, while some cases reportedly occur de novo (i.e., an individual with a pathogenic variant has parents who do not have it); however, that individual now has a 50% risk of passing it on to their offspring.

Guidelines for surveillance, clinical evaluation, and treatment of MEN1 are published by the National Comprehensive Cancer Network (NCCN; National Comprehensive Cancer Network. Neuroendocrine Tumors. Version 2.2016, Accessed August 16, 2017) and by Thakker et al. (PMID: 22723327).

NCCN Guidelines:
Clinical evaluation at diagnosis of MEN1

  • Parathyroid: serum calcium and 25-OH vitamin D
  • Pancreatic neuroendocrine: multiphasic CT or MRI
  • Pituitary: pituitary MRI
  • Bronchial/thymic: multiphasic CT or MRI
  • Biochemical evaluation as clinically indicated
  • Genetic counseling and testing

As appropriate:

  • Pituitary: neck ultrasound, parathyroid sestamibi scan
  • Pancreatic neuroendocrine: endoscopic ultrasound, somatostatin receptor scintigraphy


  • Parathyroid:
    • Subtotal parathyroidectomy or total parathyroidectomy with autotransplantation:
      • with or without cryopreservation of the parathyroids
      • with or without thymectomy
  • Pancreatic neuroendocrine:
    • Surgical management similar to sporadic pancreatic neuroendocrine tumors
    • However, surgery in multifocal tumor setting is controversial and can be considered in the following scenarios:
      • symptomatic functional tumors refractory to medical management
      • tumor larger than 1-2 cm in size
      • tumor with relatively rapid growth over 6-12 months
  • Pituitary:
    • Consider referral to endocrinology for further workup
  • Bronchial/thymic:
    • Refer to NCCN guidelines for more information


  • Parathyroid:
    • Serum calcium annually
    • If calcium rises:
      • serum PTH and 25-OH vitamin D
      • re-image with neck ultrasound and/or parathyroid sestamibi scan
      • consider cross-sectional neck CT or MRI
  • Pancreatic neuroendocrine:
    • Follow previously elevated serum hormones or as symptoms indicate
    • Consider cross-sectional imaging with CT or MRI every 1-3 years
    • Consider serial endoscopic ultrasound
  • Pituitary:
    • MRI of pituitary every 3-5 years
    • Prolactin, IGF-1, and other previously abnormal pituitary hormones every 3-5 years or as symptoms indicate
  • Bronchial/thymic:
    • Consider cross-sectional chest imaging with CT or MRI every 1-3 years

Professional Consensus Guidelines (Thakker et al. PMID: 22723327)

Screening in individuals at high risk of developing MEN1

TumorAge to begin (yr)Biochemical test: plasma or serum (annually)Imaging test (time interval)
Parathyroid8Calcium, PTHNone
Pancreatic neuroendocrine:   
20Gastrin (± gastric pH)None
5Fasting glucose, insulinNone
    Other primitive neuroectodermal tumor
<10Chromogranin-A, pancreatic polypeptide, glucagon, vasocative intestinal peptideMRI, CT, or endoscopic ultrasound (annually)
Pituitary5Prolactin, IGF-IMRI (every 3 years)
Thymic or bronchial carcinoid15NoneCT or MRI (every 1-2 years)
Adrenal<10None unless symptoms or signs of functioning tumor and/or tumor >1cm are identified on imaging MRI or CT (annually with pancreatic imaging)

Table adapted from PMID: 22723327

Treatment of MEN1-associated tumors
Parathyroid tumors:

  • Recommended: Conventional open bilateral exploration with subtotal parathyroidectomy (at least 3.5 glands) or total parathyroidectomy
  • Suggested: Concurrent transcervical thymectomy at the time of surgery
  • Consider: Total parathyroidectomy with autotransplantation

Pancreatic neuroendocrine tumors:

  • Recommended: A histopathologist with expertise in neuroendocrine tumors should review all tumor tissues. Tumors should be classified according to the World Health Organization 2010 classification, Union for International Cancer Control TNM (7th edition), and the European Neuroendocrine Tumor Society site-specific T-staging system.
  • Gastrinoma:
    • Consider: Surgery for non-metastasizing gastrinoma arising within the pancreas
    • Suggested: Medical management using proton-pump inhibitors for patients with multiple small submucosal duodenal gastrinomas (multifocal tumors)
    • Consider: Local excision of multifocal tumors with lymph node dissection, duodenectomy, or less commonly duodenopancreatectomy in experienced surgical centers; whipple pancreaticoduodenectomy is not suggested
    • Recommended: Medical therapies including proton-pump inhibitors and somatostatin analogs to suppress hyperacidity
    • Suggested: Periodic gastroscopic surveillance for those with hypergastrinemia for the identification of peptic ulcer disease and gastric carcinoid
  • Nonfunctioning pancreatic tumors:
    • Consider: Surgery for tumors that are >1 cm and/or demonstrate significant growth over 6-12 months
  • Nonresectable pancreatic neuroendocrine tumors:
    • Recommended: Somatostatin analogs, biotherapy, targeted radionuclide therapy, locoregional treatments, and chemotherapy
    • Recommended: Chemotherapy for nonresectable or metastatic tumors; consider sunitinib and everolimus for nonresectable or metastatic progressive well-differentiated tumors

Pituitary tumors:

  • Recommended: Appropriate medical therapy (e.g., dopamine agonists for prolactinoma; octreotide or lanreotide for somatotrophinomas) or selective transsphenoidal surgical hypophysectomy, with radiotherapy reserved for residual unresectable tumor tissue

Bronchial/thymic/gastric neuroendocrine tumors:

  • Recommended: Curative surgery, if possible, for thymic and bronchial carcinoid tumors
  • Suggested: Radiotherapy and chemotherapy for advanced thymic and bronchial carcinoid tumors
  • The optimal treatment of type II gastric carcinoids has not been established. Small (<10 mm) lesions may remain under endoscopic surveillance. Larger tumors require endoscopic resection or local resection with partial or total gastrectomy. Indications for somatostatin analogs in the treatment of type II gastric carcinoids are not defined.

Adrenal tumors:

  • Recommended: Surgery for functioning tumors (e.g., primary hyperaldosteronism or hypercortisolism), and nonfunctioning tumors with atypical features, size >4 cm, or significant growth over a 6-month interval

An individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors including personal medical history, family history, as well as available genetic information that may result in a personalized plan for cancer prevention and surveillance.

It is advantageous to know if a pathogenic variant in the MEN1 gene is present as medical management recommendations can be implemented. At-risk relatives can be identified, allowing pursuit of a diagnostic evaluation. In addition, the available information regarding hereditary cancer susceptibility genes is constantly evolving and more clinically relevant data is likely to become available in the near future. Awareness of this cancer predisposition allows patients and their providers to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information, inform at-risk family members, and diligently follow condition-specific screening protocols.

Additional references

Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Neuroendocrine Tumors V.2.2016. © National Comprehensive Cancer Network, Inc 2016. All rights reserved. Accessed August 16, 2017. To view the most recent and complete version of the guideline, go online to NCCN.org. National Comprehensive Cancer Network®, NCCN®, NCCN Guidelines®, and all other NCCN content are trademarks owned by the National Comprehensive Cancer Network, Inc.

Review date: August 2017

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

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
MEN1 NM_130799.2