Investigation of genetic factors on etiology of familial melanoma syndrome: evaluation of copy number variation (CNV) and exome sequencing

• Grant number: 12/21932-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2013
• End date: November 30, 2015
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Ana Cristina Victorino Krepischi
• Grantee: Felipe Fidalgo de Carvalho
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil

Abstract

Cancer is a complex disease arising from an accumulation of multiple and successive somatic mutations, resulting in modifications at gene functions that act in specific molecular pathways such as cell cycle control, apoptosis, differentiation and angiogenesis. However, some individuals of population show higher predisposition to develop specific types of cancer due the presence of a constitutional mutation in their genomes. The genes already identified as cancer predisposition do not explain most part of cases of familial groups of cancer, indicating the existence of genetic factors that remains unknown. Mutations at locus CDKN2A correspond to 20-40% of familial melanoma cases and mutations on CDK4 gene are detected on a limited number of families; therefore, other genes might be involved on development of disease in patients who do not show mutation in this predisposition main gene. The identification of new associated genes to higher predisposition to melanoma is crucial to better understanding of disease and also to identification of risk individuals. In this project, we propose the genome study of patients from affected families by the familial melanoma syndrome, negatives to mutations at locus CDKN2A and CDK4 gene. We are going to investigate the role of structural variations of human genome known as copy number variations (CNVs) at etiology of familial melanoma, and we are also going to perform an exploratory analysis in a subgroup of these patients, aiming to identify pathogenic mutations through complete exome sequencing. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FIDALGO, FELIPE; GOMES, ELIMAR ELIAS; FACURE, LUCIANA MOREDO; DA SILVA, FELIPE CARNEIRO; CARRARO, DIRCE MARIA; SOARES DE SA, BIANCA COSTA; DUPRAT NETO, JOAO PEDREIRA; VICTORINO KREPISCHI, ANA CRISTINA. Association of melanoma with intraepithelial neoplasia of the pancreas in three patients. Experimental and Molecular Pathology, v. 97, n. 1, p. 144-147, AUG 2014. (13/07480-8, 12/21932-6, 08/57887-9)

FIDALGO, FELIPE; RODRIGUES, TATIANE CRISTINA; SILVA, AMANDA GONCALVES; FACURE, LUCIANA; SOARES DE SA, BIANCA COSTA; DUPRAT, JOAO PEDREIRA; ACHATZ, MARIA ISABEL; ROSENBERG, CARLA; CARRARO, DIRCE MARIA; VICTORINO KREPISCHI, ANA CRISTINA. Role of rare germline copy number variation in melanoma-prone patients. FUTURE ONCOLOGY, v. 12, n. 11, p. 1345-1357, JUN 2016. (12/21932-6, 08/57887-9)

FIDALGO, FELIPE; RODRIGUES, TATIANE CRISTINA; PINILLA, MABEL; SILVA, AMANDA GONCALVES; DO SOCORRO MACIEL, MARIA; ROSENBERG, CARLA; DE ANDRADE, VICTOR PIANA; CARRARO, DIRCE MARIA; VICTORINO KREPISCHI, ANA CRISTINA. Lymphovascular invasion and histologic grade are associated with specific genomic profiles in invasive carcinomas of the breast. TUMOR BIOLOGY, v. 36, n. 3, p. 1835-1848, MAR 2015. (12/21932-6, 08/57887-9, 11/24007-9)