Comprehensive Analysis of MEN1 Mutations and Their Role in Cancer

Abstract

MENIN is a scaffold protein encoded by the MEN1 gene that functions in multiple biological processes, including cell proliferation, migration, gene expression, and DNA damage repair. MEN1 is a tumor suppressor gene, and mutations that disrupts MEN1 function are common to many tumor types. Mutations within MEN1 may also be inherited (germline). Many of these inherited mutations are associated with a number of pathogenic syndromes of the parathyroid and pancreas, and some also predispose patients to hyperplasia. In this study, we cataloged the reported germline mutations from the ClinVar database and compared them with the somatic mutations detected in cancers from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. We then used statistical software to determine the probability of mutations being pathogenic or driver. Our data show that many confirmed germline mutations do not appear in tumor samples. Thus, most mutations that disable MEN1 function in tumors are somatic in nature. Furthermore, of the germline mutations that do appear in tumors, only a fraction has the potential to be pathogenic or driver mutations.

Identification of New Molecular Biomarkers in Ovarian Cancer Using the Gene Expression Profile

“…The tumor suppressor gene MEN1 encodes a protein called menin, which is related to many biological processes, including cell proliferation, migration, gene expression, and repair of DNA damage. The MEN1 gene is responsible for the occurrence of multiple proliferative changes (hyperplasia, adenomas, and carcinomas) [37]. In our study, we showed a decrease in the mRNA and protein level for MEN1 in patients with ovarian cancer compared with healthy controls.…”

Identification of New Molecular Biomarkers in Ovarian Cancer Using the Gene Expression Profile

“…The tumor suppressor gene MEN1 encodes a protein called menin, which is related to many biological processes, including cell proliferation, migration, gene expression, and repair of DNA damage. The MEN1 gene is responsible for the occurrence of multiple proliferative changes (hyperplasia, adenomas, and carcinomas) [37]. In our study, we showed a decrease in the mRNA and protein level for MEN1 in patients with ovarian cancer compared with healthy controls.…”

Evaluating the role of MEN1 gene expression and its clinical significance in breast cancer patients

“…MEN1 mutations are frequent and aggressive C-terminus of MEN1 protein forms the finger domain and contains three nucleus localizing sequences. The disruption in C-terminus is known to have a vital role in tumorigenesis [ 9 , 26 , 27 ]. However, our automated sequencing analysis did not show any mutation in the exons coding this domain of MEN1 gene ( Fig 6 ).…”

Epidemiology and clinical outcomes of clinically suspected multiple endocrine neoplasia type 1 in South Korea: a nationwide cohort study

“…Similarly, the high rate of pancreatic cancer may reflect misclassification, where aggressive DPNENs characteristic of MEN1 are potentially miscoded as pancreatic adenocarcinomas ( 20 ). These observations underscore the need for further research incorporating comprehensive genetic analyses and detailed clinical data to elucidate the true cancer risk profile in MEN1 patients and to understand potential ethnic or regional variations in tumor manifestation ( 28 ).…”

Identification of New Molecular Biomarkers in Ovarian Cancer Using the Gene Expression Profile

“…The tumor suppressor gene MEN1 encodes a protein called menin, which is related to many biological processes, including cell proliferation, migration, gene expression, and repair of DNA damage. The MEN1 gene is responsible for the occurrence of multiple proliferative changes (hyperplasia, adenomas, and carcinomas) [37]. In our study, we showed a decrease in the mRNA and protein level for MEN1 in patients with ovarian cancer compared with healthy controls.…”

Evaluating the role of MEN1 gene expression and its clinical significance in breast cancer patients

“…MEN1 mutations are frequent and aggressive C-terminus of MEN1 protein forms the finger domain and contains three nucleus localizing sequences. The disruption in C-terminus is known to have a vital role in tumorigenesis [ 9 , 26 , 27 ]. However, our automated sequencing analysis did not show any mutation in the exons coding this domain of MEN1 gene ( Fig 6 ).…”

Epidemiology and clinical outcomes of clinically suspected multiple endocrine neoplasia type 1 in South Korea: a nationwide cohort study

“…Similarly, the high rate of pancreatic cancer may reflect misclassification, where aggressive DPNENs characteristic of MEN1 are potentially miscoded as pancreatic adenocarcinomas ( 20 ). These observations underscore the need for further research incorporating comprehensive genetic analyses and detailed clinical data to elucidate the true cancer risk profile in MEN1 patients and to understand potential ethnic or regional variations in tumor manifestation ( 28 ).…”

Identification of New Molecular Biomarkers in Ovarian Cancer Using the Gene Expression Profile

“…The tumor suppressor gene MEN1 encodes a protein called menin, which is related to many biological processes, including cell proliferation, migration, gene expression, and repair of DNA damage. The MEN1 gene is responsible for the occurrence of multiple proliferative changes (hyperplasia, adenomas, and carcinomas) [37]. In our study, we showed a decrease in the mRNA and protein level for MEN1 in patients with ovarian cancer compared with healthy controls.…”

Evaluating the role of MEN1 gene expression and its clinical significance in breast cancer patients

“…MEN1 mutations are frequent and aggressive C-terminus of MEN1 protein forms the finger domain and contains three nucleus localizing sequences. The disruption in C-terminus is known to have a vital role in tumorigenesis [ 9 , 26 , 27 ]. However, our automated sequencing analysis did not show any mutation in the exons coding this domain of MEN1 gene ( Fig 6 ).…”

Epidemiology and clinical outcomes of clinically suspected multiple endocrine neoplasia type 1 in South Korea: a nationwide cohort study

“…Similarly, the high rate of pancreatic cancer may reflect misclassification, where aggressive DPNENs characteristic of MEN1 are potentially miscoded as pancreatic adenocarcinomas ( 20 ). These observations underscore the need for further research incorporating comprehensive genetic analyses and detailed clinical data to elucidate the true cancer risk profile in MEN1 patients and to understand potential ethnic or regional variations in tumor manifestation ( 28 ).…”