| Grant number: | 13/24633-2 |
| Support Opportunities: | Regular Research Grants |
| Start date: | November 01, 2014 |
| End date: | April 30, 2017 |
| Field of knowledge: | Biological Sciences - Genetics - Human and Medical Genetics |
| Principal Investigator: | Edenir Inêz Palmero |
| Grantee: | Edenir Inêz Palmero |
| Host Institution: | Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil |
| Associated researchers: | André Lopes Carvalho ; Cristovam Scapulatempo Neto ; Daniel Onofre Vidal ; Dirce Maria Carraro ; Elisa Napolitano e Ferreira ; Lucas Tadeu Bidinotto ; Matias Eliseo Melendez ; Patricia Ashton Prolla ; Raul Torrieri ; Rui Manuel Vieira Reis |
Abstract
Breast cancer (BC) is considered a public health problem, being 5% to 10% hereditary. The identification of individuals at risk for hereditary cancer is important because: 1) affected individuals have a much higher cumulative cancer risk, 2) relatives of an affected individual may be at-risk for hereditary cancer, and 3) the existence of intensive screening and preventive intervention measures that can significantly lowers the risk of cancer in mutation carriers. However, although there are about 30 genetic loci associated with an increased predisposition/susceptibility to hereditary breast cancer (HBC), for a large proportion of cases (about 70%), the genetic cause remains unknown. Thus, given the high risk for cancer develpment of these individuals/families and the knowledge required about which mutation is causing the phenotype in order that preventive strategies can be devised, the main objective of this proposal is to perform a comprehensive molecular characterization of a group of 40 unrelated women (40 families) with high risk for HBC and negative for germline deleterious BRCA1/BRCA2 mutations. Aiming to homogenize the sample group, it was subdivided into: (a) 20 women with a personal history of BC and the presence of at least four BC cases before the age of 55 years old, at least two cancer affected generations, no cases of male BC and ovarian cancer, and (b) 20 women with breast and/or ovarian cancer and the presence of at least 4 BC cases and 1 ovarian cancer, at least two generations affected and no male BC. The strategies to be employed are: (i) next generation sequencing of constitutive DNA (analysis of the coding region of a gene panel classically associated with hereditary breast cancer), (ii) exome DNA sequencing (obtained from peripheral blood), (iii) analysis of the presence of microscopic and submicroscopic chromosomal alterations (in constitutive and tumoral DNA) by aCGH and (iv) large escale analysis of epigenetic changes (metiloma of normal and tumoral breast tissue). We hope, therefore, that this design allows for a greater understanding of the genetic and epigenetic mechanisms related to HBC, enabling a growing number of patients / families with a history suggestive of hereditary cancer may benefit from a specialized and personalized treatment. (AU)
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