What is the role of MEN 1 in the etiology of carcinoid tumors?

Updated: Feb 12, 2019
  • Author: Cameron K Tebbi, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Answer

MEN 1 is an autosomal dominant disorder characterized by the occurrence of multiple tumors, particularly in the pancreatic islets, parathyroid and pituitary glands, and neuroendocrine tumors. [58]

  • Germline mutations in the MEN 1 gene can be identified in the general population.

  • Multiple carcinoid tumors occurring in association with MEN 1 have been reported. [59]

  • Although the MEN 1 gene locus is known to be involved in neuroendocrine tumors, the genetic events underlying the neoplastic process are basically unknown.

  • Familial cases other than those associated with MEN 1 are rare, but do occur. [60]

  • In several studies, loss of heterozygosity (LOH) at the MEN 1 locus has been reported. [61, 62, 63, 64, 65, 66]

  • Genetic abnormalities involving chromosome 11 are most common. These can be seen as a part of MEN 1 or independent of MEN 1 abnormalities. [65, 66] In 5 of 9 typical carcinoid tumors of the lung, 3 distinct regions of allelic loss were identified at bands 11q13.1 (D11S1883), 11q14.3-11q21 (D11S906), and 11q25 (D11S910).

  • Some atypical carcinoids have LOH at band 11q13 between markers PYGM and D11S937 and at bands 11q14.3-11q21 (D11S906), 11q23.2-23.3 (D11S939), and 11q25 (D11S910).

  • The region of band 11q13 bearing the MEN 1 gene can also be affected in some atypical carcinoid tumors more than it is in typical carcinoid tumors. Therefore, band 11q13 appears to be important in these tumors. Aggressive atypical carcinoid tumors, defined by high mitosis, vascular invasion and organ metastasis, also appear to have more allelic losses than other tumors.

  • The MEN 1 gene is located on band 11q13 and likely functions as a tumor-suppressor gene. In a study of 46 sporadically occurring tumors, 78% had LOH at this site, with almost the entire allele missing in 5 patients. In the remaining cases, genetic heterozygosity had a discontinuous pattern. Some have postulated that sporadically occurring carcinoid tumors evolve after inactivation of a tumor-suppressor gene on chromosome 11 as well as genetic mutations that affect DNA-mismatch repair.


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