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

• Grant number: 09/06552-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2009
• End date: July 31, 2011
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sergio Pereira de Almeida Toledo
• Grantee: Michelle Buscarilli de Moraes
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

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 MEN1 in a germinative level, however whether they are inactivated in tumors of patients with MEN1 mutation is so far not clarified. In the current study, we will use molecular biology techniques to evaluate possible occurrence of LOH in loci of these novel MEN1-related tumor suppressor genes CDKN1A, CDKN1B, CDNK2B, CDKN2C and AIP, in tumors from patients previously diagnosed clinically and genetically with MEN1 by our group in the Hospital das Clinical Division of Endocrinology, and investigated LIM-25 (Genetics Unit of Endocrinology).Our current study, at the level of Master degree, is a continuation and expansion of a previous project at Scientific Initiation degree of the student (2007-2008; Pibic), in which it was characterized 11q13 LOH in tumors from several patients with MEN1.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MORAES, Michelle Buscarilli de. Analysis of the status of somatic and p27Kip1 genes in tumors from patients with multiple endocrine neoplasia type 1. 2012. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.