Multiple Endocrine Neoplasia Type1 (MEN1)

Multiple Endocrine Neoplasia Type 1(MEN1) is an inherited cancer syndrome characterized by the occurrence of endocrine and non-endocrine tumors mainly involving the parathyroid gland, anterior pituitary gland, and the pancreas. 

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Multiple Endocrine Neoplasia Type 1(MEN1) is an inherited cancer syndrome characterized by the occurrence of endocrine and non-endocrine tumors mainly involving the parathyroid gland, anterior pituitary gland, and the pancreas. 

Germline mutations in the MEN1 gene cause a predisposition to develop tumors associated with this condition. Mutations in MEN1 are detected in approximately 80-90% of affected individuals.

Disease Name 
Multiple Endocrine Neoplasia Type 1
Disease Information 

Multiple endocrine neoplasia type 1 (MEN1), also known as Wermer syndrome, is an inherited cancer syndrome characterized by the occurrence of endocrine and non-endocrine tumors mainly involving the parathyroid, anterior pituitary and the pancreas. The most common endocrine tumors include, parathyroid adenomas, prolactinomas, and gastrinomas.1 Non-endocrine features include facial angiofibromas, collagenomas, and lipomas.1-3 Generally, primary hyperparathyroidism is the first clinical manifestation in up to 100% of patients by the age of 40, with a typical age of onset between 20-25 years old.4,5 Twenty percent of individuals diagnosed with familial isolated hyperparathyroidism have mutations in the MEN1 gene.

MEN1 is inherited in an autosomal dominant manner and is caused by germline mutations in the tumor suppressor gene MEN1. Germline mutations in this gene cause a predisposition to develop tumors associated with this condition. The incidence of MEN1 is estimated to be 1/30,000, affecting all ethnic backgrounds worldwide.

Gene sequence and gross deletion/duplication analyses are available. Mutations in MEN1 are detected in approximately 80-90% of affected individuals. To date, partial and whole-gene deletions/duplications have accounted for up to 4-6% of pathogenic mutations identified in large MEN1 cohorts and over 5% of all MEN1 mutations listed in The Human Gene Mutation Database (HGMD).6-8

Testing Benefits & Indication 

Genetic testing enables identification of individuals who are at increased risk of cancer associated with MEN1 mutations. It is useful in the confirmation of diagnosis in symptomatic individuals.  Although approximately one-third of MEN1 patients will die from an MEN1-related cancer, treatment options are available for disease management, including surgical removal of endocrine tumors, various drug treatments and radiation therapy.9,10  Specific mutation analysis for individual MEN1 mutations is available for relatives of patients with known mutations in MEN1.

Test Description 

MEN1 coding exons1-9 and well into the 5’ and 3’ ends of all the introns and untranslated regions are analyzed by sequencing. Gross deletion/duplication analysis determines gene copy number for coding exons1-9.Clinically significant intronic findings beyond 5 base pairs are always reported. Intronic variants of unknown or unlikely clinical significance are not reported beyond 5 base pairs from the splice junction. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using standardized methodology and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology, using long biotinylated oligonucleotide probes followed by polymerase chain reaction (PCR) and next generation sequencing (NGS). Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Reportable small insertions and deletions, potentially homozygous variants, variants in regions complicated by pseudogene interference, and single nucleotide variant calls not satisfying 100x depth of coverage and 40% het ratio thresholds are verified by Sanger sequencing.11  Gross deletion/duplication analysis of MEN1 using read-depth from NGS data is also performed. Any copy number changes detected by NGS are confirmed by targeted chromosomal microarray and/or multiplex ligation-dependent probe amplification (MLPA).

Mutation Detection Rate 

Mutations in the MEN1 gene account for 80-90% of individuals affected with familial MEN, as the index case in the family (clinical sensitivity).1  Ambry's MEN1 analysis can detect >99.9% of described mutations in the gene, when present (analytic sensitivity).

Specimen Requirements 

Complete specimen requirements are available here or by downloading the PDF found above in the Quick Links section at the top of this page.

Turnaround Time 
Test Code Technique CALENDAR DAYS
2646 MEN1 Gene Sequence and Deletion/Duplication Analysis 14-21 

 

Specialty 
Genes 
MEN1
References 
  1. Brandi ML, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001; 86: 5658-5671. [PMID: 11739416]
  2. Asgharian B, et al. Cutaneous tumors in patients with multiple endocrine neoplasm type 1 (MEN1) and gastrinomas: prospective study of frequency and development of criteria with high sensitivity and specificity for MEN1. J Clin Endocrinol Metab. 2004; 89 (11): 5328-5336. [PMID: 15531478]
  3. Darling TN, et al. Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1. J Arch Dermatol. 1997; 133: 853-857. [PMID: 9236523]
  4. urgess JR, et al. Osteoporosis in multiple endocrine neoplasia type 1: severity, clinical significance, relationship to primary hyperparathyroidism, and response to parathyroidectomy. Arch Surg.1999; 134: 1119-1123. [PMID: 10522858]
  5. Tichomirowa MA, et al. Familial pituitary adenomas. J Intern Med. 2009; 266: 5-18. [PMID: 19522822]
  6. Cebrian A et al. Mutational and gross deletion study of the MEN1 gene and correlation with clinical features in Spanish patients. J Med Genet. 2003;40(5):e72. [PMID: 12746426]
  7. Tham E et al. Clinical testing for mutations in the MEN1 gene in Sweden: a report on 200 unrelated cases. J Clin Endocrinol Metab. 2007;92(9):3389-95. [PMID: 17623761]
  8. Stenson PD, et al. Human Gene Mutation Database (HGMD): 2003 update. Hum Mutat. 2003;21:577-581). [PMID: 12754702]
  9. Agarwal SK, et al. The MEN1 gene and pituitary tumours. J Horm Res. 2009; 71: 131-138. [PMID: 19407509]
  10. Gagel RF, et al. Williams Textbook of Endocrinology. 2007:1705-1746.
  11. Mu W, et al. Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing. J Mol Diagn. 2016. 18(6):923-932.