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| Author(s): |
Michelle Buscarilli de Moraes
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2012-06-06 |
| Examining board members: |
Sergio Pereira de Almeida Toledo;
Maria Candida Barisson Villares Fragoso;
Osmar Monte
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| Advisor: | Sergio Pereira de Almeida Toledo |
| Abstract | |
Approximately 80% of cases with multiple endocrine neoplasia type 1 (MEN1) harbor a germline mutation in the tumor suppressor gene MEN1, which predisposes these patients to tumors comprehending the parathyroid and pituitary glands, endocrine pancreas and others non-endocrine tumors. The tumorigenesis of the more than 20 different types of tumors already described in the MEN1 syndrome occurs due to a MEN1 germline mutation associated with a second mutational event in the cells of these tissues, leading to loss of heterozygosity (LOH) of the MEN1 gene locus (11q13) and therefore inactivation of tumor suppressor protein encoded by this gene, MENIN protein. Recently, germline mutations in other genes have been described in cases with MEN1 without any detectable mutations in the MEN1 gene. These novel genes (CDKN1A, CDKN1B, CDNK2B and CDKN2C) encode proteins involved in the control of the cell cycle (p21, p27, p15 and p18), called cyclin dependent kinases inhibitors. Another gene, called AIP, which encodes a chaperon protein with the same name, was recently described associated with MEN1 phenotypes. These data described a role for these novel genes in the germline level, however whether they are inactivated in tumors of patients with MEN1 mutation is so far not clarified. The present study investigated for the first time, the somatic status of p27KIP1 gene mutation in patients with MEN1 and identified four possible loss of heterozygosity (LOH) in tumors of the parathyroid and pancreas, suggesting that in addition 11q13-LOH, MEN1 tumors may suffer rare loss additional tumor suppressor gene p27KIP1. These are the first evidence in the literature of a process of tumorigenesis in MEN1 multi-step, involving three genetic events: 1-MEN1germlinemutation; 2-11q13LOH; 3-Loss of somatic tumor suppressor gene p27Kip1/CDKN1B (AU) | |
| FAPESP's process: | 09/06552-0 - Loss of heterozygosity analysis in tumors from patients with Multiple Endocrine Neoplasia type 1: study of the MEN1 gene and novel genes recently associated with this syndrome |
| Grantee: | Michelle Buscarilli de Moraes |
| Support Opportunities: | Scholarships in Brazil - Master |