This test analyzes the MEN1 gene, which is associated with multiple endocrine neoplasia type 1 (MEN1). MEN1 is a cancer predisposition condition that causes an increased risk of developing neuroendocrine tumors of the parathyroid, anterior pituitary, and pancreas.
Genetic testing of this gene 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.
MEN1 can also be ordered as part of a broader panel to test for different types of hereditary cancer, including colon cancer. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered for no additional charge.
MEN1 syndrome is associated with a high risk of developing tumors of the endocrine system, primarily in the parathyroid gland, anterior pituitary, adrenal gland and pancreas. Other tumors may also occur, including gastrinomas and carcinoid tumors. Symptoms of MEN1 usually begin in adulthood, with parathyroid disease manifesting by age of 50 in nearly all affected individuals. Symptoms can vary significantly among family members, and affected individuals may present with different tumor types or symptoms. Other non-endocrine tumors may also be present, including benign thyroid lesions (such as goiter), skin tumors (angiofibromas) and lipomas (benign fatty tissue tumors).
Lifetime cancer risks in individuals with MEN1 are very high: Parathyroid tumors develop in nearly all affected individuals by age 50 and are the first manifesting feature in 90% of cases.
|Tumor type||Tumor/cancer risk|
|Pancreatic islet cell||30%-70%|
|Thyroid (including goiter)||25%|
|Carcinoid (thymic, bronchial, gastric)||10%|
Genetic testing identifies pathogenic variants in approximately 80%-90% of individuals who meet clinical diagnostic criteria for MEN1 and have a family history of MEN1-related tumors. A pathogenic variant is found in 65% of cases of individuals who meet diagnostic criteria but have no family history.
MEN1 is inherited in an autosomal dominant pattern. Most cases are inherited, but approximately 10% occur as the result of a spontaneous de novo mutation.
Testing for MEN1 may be considered for individuals with a personal and/or family history of features, including:
Clinical practice guidelines for MEN1 have been proposed:
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|