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The biologic and clinical characterization of the RAS-MAPK and PI3K-AKT pathways in cutaneous and mucosal melanomas among Brazilians and comparison with patients of the United States of America

Grant number: 12/04194-1
Support Opportunities:Regular Research Grants
Duration: October 01, 2012 - September 30, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Vinicius de Lima Vazquez
Grantee:Vinicius de Lima Vazquez
Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
Associated researchers:Jeremy Andrew Squire ; Rui Manuel Vieira Reis


Melanoma is the most aggressive form of skin cancer, with high clinical and molecular complexity and heterogeneity and raising incidence in Brazil and the World. The identification of frequent mutations has provided a strong impetus to determine the molecular characteristics of each melanoma patient. Previous studies have demonstrated that patterns of genetic mutations and alteration of the number of DNA copy are different from different melanoma subtypes. Mutation in the BRAF/NRAS genes correlated to the metastasis patterns and survival. There is little data about the molecular characteristics of melanoma from Brazil. The molecular definition and clinical characteristics will allow objective comparison with the results obtained from other countries. Previous research has demonstrated that metastatic patients from different populations may present distinct clinical course and mutated oncogenes may have frequencies markedly different among patients from different regions/ethnics. However, currently there is little known about the prevalence and prognostic significance of genetic alterations in melanoma in different parts of the world. The central hypothesis of this study is that clinicopathologically-defined groups of melanomas from Brazil and the United States have different molecular characteristics, and that such differences correlate with different clinical outcomes. The cellular melanoma culture will build a platform and allow the study of genetic and biological aspects including pharmacological tests with antineoplasic drugs with local cell lines, in a more realistic scenario. (AU)

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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)
PINHEIRO, CELINE; MIRANDA-GONCALVES, VERA; LONGATTO-FILHO, ADHEMAR; VICENTE, ANNA L. S. A.; BERARDINELLI, GUSTAVO N.; SCAPULATEMPO-NETO, CRISTOVAM; COSTA, RICARDO F. A.; VIANA, CRISTIANO R.; REIS, RUI M.; BALTAZAR, FATIMA; et al. The metabolic microenvironment of melanomas: Prognostic value of MCT1 and MCT4. CELL CYCLE, v. 15, n. 11, p. 1462-1470, . (15/25351-6, 12/04194-1)
FAIAO-FLORES, F.; ALVES-FERNANDES, D. K.; PENNACCHI, P. C.; SANDRI, S.; VICENTE, A. L. S. A.; SCAPULATEMPO-NETO, C.; VAZQUEZ, V. L.; REIS, R. M.; CHAUHAN, J.; GODING, C. R.; et al. Targeting the hedgehog transcription factors GLI1 and GLI2 restores sensitivity to vemurafenib-resistant human melanoma cells. Oncogene, v. 36, n. 13, p. 1849-1861, . (12/04194-1, 15/10821-7, 13/05172-4, 14/24400-0)
SILVA ALMEIDA VICENTEL, ANNA LUIZA; BIANCHINI, RAQUEL ALVES; LAUS, ANA CAROLINA; MACEDO, GRAZIELA; REIS, RUI MANUEL; VAZQUEZ, VINICIUS DE LIMA. Comparison of protocols for removal of melanin from genomic DNA to optimize PCR amplification of DNA purified from highly pigmented lesions. HISTOLOGY AND HISTOPATHOLOGY, v. 34, n. 9, p. 1089-1096, . (17/09612-0, 12/04194-1, 16/15941-3)

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