Multiple Endocrine Neoplasia Comprehensive

  • Panel Description
  • Test Description
  • CPT Codes
  • Gene Descriptions

Panel Description

Multiple Endocrine Neoplasia (MEN)
MEN Type 1
MEN Type 2
MEN Type 4
Familial Medullary Thyroid Carcinoma (FMTC)
Fulgent’s Multiple Endocrine Neoplasias Comprehensive Panel looks at genes that are commonly associated with increased risk for hereditary multiple endocrine neoplasias and other related conditions. This test includes both well-established multiple endocrine neoplasia susceptibility genes, as well as candidate genes with limited evidence of an association with multiple endocrine neoplasia specific cancers.

This panel may be appropriate for individuals with a personal or family history suggestive of hereditary multiple endocrine neoplasia. Common features can include but are not limited to multiple tumors (neoplasias- benign or malignant) in the endocrine system (parathyroid glands, pituitary glands, pancreas, adrenal glands and medullary thyroid) and/or other organs/tissues. Biochemical testing indicating irregular (excessive or reduced) hormone levels or elevated calcium levels in the blood may also be suggestive of tumors in these glands. Affected individuals may also exhibit physical features including cutaneous (skin) findings such as multiple lipomas (fatty tissues), angiomas (small growths), cafe-au-lait spots (flat, pigmented birthmarks) or “marfanoid” habitus. Additional features that may be relevant are cancers in the family with an age of onset before 50 years, more than one primary cancer in a single individual, and multiple affected family members. This test is designed to detect individuals with a germline pathogenic variant and is not validated to detect mosaicism below the level of 20%. It should not be ordered on tumor tissue.

Patients identified with a multiple endocrine neoplasia can benefit from increased surveillance and preventative steps to better manage their risk for cancer. Information obtained from candidate gene testing may potentially be helpful in guiding clinical management in the future. Close relatives of patients who have a pathogenic variant identified by this panel may also be at risk. Children, siblings, and/or parents of individuals identified with pathogenic variants could have as high as a 50% chance of having the same variant, therefore also being at an increased risk for multiple endocrine neoplasia. If an inherited susceptibility is found, your patient's family members can be tested to help define their risk.

Test Description

  • Sequencing
  • Del/Dup
  • Rush / STAT
  • Exclude VUS
2 - 3 weeks
Call for details
AIP, CASR, CDC73, CDKN1B, MEN1, RET ( 6 genes )
99% at 50x
Blood (two 4ml EDTA tubes, lavender top) or Extracted DNA (3ug in EB buffer) or Buccal Swab or Saliva (kits available upon request)
Test results and variant interpretation are based on the proper identification of the submitted specimen and use of correct human reference sequences at the queried loci. In very rare instances, errors may result due to mix-up or co-mingling of specimens. Positive results do not imply that there are no other contributions, genetic or otherwise, to the patient's phenotype, and negative results do not rule out a genetic cause for the indication for testing. Result interpretation is based on the collected information and Alamut annotation available at the time of reporting. This assay is not designed or validated for the detection of mosaicism. DNA alterations in regulatory regions or deep intronic regions (greater than 20bp from an exon) will not be detected by this test. There are technical limitations on the ability of DNA sequencing to detect small insertions and deletions. Our laboratory uses a sensitive detection algorithm, however these types of alterations are not detected as reliably as single nucleotide variants. Rarely, due to systematic chemical, computational, or human error, DNA variants may be missed. Although next generation sequencing technologies and our bioinformatics analysis significantly reduce the confounding contribution of pseudogene sequences or other highly-homologous sequences, sometimes these may still interfere with the technical ability of the assay to identify pathogenic variant alleles in both sequencing and deletion/duplication analyses. Deletion/duplication analysis can identify alterations of genomic regions which are a single exon in size. When novel DNA duplications are identified, it is not possible to discern the genomic location or orientation of the duplicated segment, hence the effect of the duplication cannot be predicted. Where deletions are detected, it is not always possible to determine whether the predicted product will remain in-frame or not. Unless otherwise indicated, in regions that have been sequenced by Sanger, deletion/duplication analysis has not been performed.

Patients with Bone Marrow Transplants:
DNA extracted from cultured fibroblasts should be submitted instead of blood/saliva/buccal samples from individuals who have undergone allogeneic bone marrow transplant and from patients with hematologic malignancy.

CPT Code 81404, 81405, 81406, 81479x2

NOTE:  The CPT codes listed on the website are in accordance with Current Procedural Terminology, a publication of the American Medical Association. CPT codes are provided here for the convenience of our clients. Clients who bill for services should make the final decision on which codes to use.
WHY ORDER THIS TEST?

Gene Descriptions

Gene Reason Reference
CDKN1B Pathogenic heterozygous variants in CDKN1B are associated with Multiple Endocrine Neoplasia, Type IV (MEN4). PubMed: 17030811, 17519308, 20824794, 22129891, 24819502, 20301710, 23652671, 26257968; OMIM: 610755
MEN1 Autosomal dominant pathogenic variants in the gene MEN1 cause Multiple endocrine neoplasia type 1 (MEN1), which is associated with an increased risk for both endocrine and non-endocrine tumors. PubMed: 11579199, 17879353, 20301710; OMIM: 131100
RET Autosomal dominant pathogenic variants in the RET gene are associated with Multiple endocrine neoplasia type 2 (MEN2), which is associated with medullary thyroid carcinoma, pheochromocytoma, and other clinical findings. PubMed: 20301434, 2906373, 8880581, 11739416; OMIM: 164761
AIP Heterozygous pathogenic variants in AIP are associated with AIP-related familial isolated pituitary adenoma (FIPA), also known as Pituitary Adenoma Predisposition (PAP) syndrome, as well as sporadic pituitary macroadenomas. PubMed: 4843205, 2773624, 8109184, 7621566, 16728643, 21753072; OMIM: 605555
CDC73 Autosomal dominant pathogenic variants in CDC73 are associated with hyperparathyroidism-jaw tumor syndrome, which increases the risk for renal tumors (hamartomas, Wilms tumor), parathyroid tumors, and ossifying fibromas of the maxilla or mandible. PubMed: 11994325, 9973288, 10770180; 27857527; OMIM: 607393
CASR There is some evidence that pathogenic variants in CASR may also be associated with chronic pancreatitis, which is a risk factor for pancreatic cancer. Additional research is needed to confirm this association, and any increased risk for cancer. PubMed: 9642634, 11807402, 14985373, 19423559; 18938753, 25400986; OMIM: 601199