Project Title: “Comprehensive Analysis of MEN1 Mutations and Their Role in Cancer”
Mentor: Ruben Petraeca, Molecular Genetics
Published paper link for more details: https://www.mdpi.com/826300
Introduction/Background: 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.
Methods: 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. COSMIC deposits both primary patient data obtained from the National Institutes of Health (NIH) The Cancer Genome Atlas (TCGA) project, as well as cell line data from the Cell Lines Project. Pathogenic investigator submitted mutations were first extracted from Variation Viewer and then were manually checked against ClinVar data to ensure that they were reported to be germline and pathogenic. Then, statistical analysis software was used to determine the probability of mutations being pathogenic or driver.
Results & Conclusion: Our data showed that only a fraction of inherited MEN1 aberrations appear as somatic mutations in tumors. Although germline MEN1 mutations contribute to the clinical pathologies of the parathyroid, thyroid, and pancreatic syndromes, we find that very few contribute to neoplasia and cancer. As neither COSMIC nor TCGA contains inherited MEN1 mutant patient data, our analysis is limited to making predictions on the contribution of these events to tumorigenesis. However, as this is a pan-cancer analysis it suggests that, if MEN1 germline mutations significantly contributed to cancer phenotypes, they would be detectable in various patient samples. We further show that, of the germline mutations that do appear in tumors, only a small fraction has the potential to be pathogenic or driver mutations. The clinical value of this data is to highlight the need for somatic testing of cancer patients with MEN1 disruptions, rather than, or at least in addition to, pedigree studies that focus on cancer pre-disposition syndromes.
Presentation Video: https://youtu.be/iJl6BDQQM5U
Poster: Comprehensive Analysis of MEN1 Mutations and Thier Role in Cancer