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Evaluation of BRAF (7q34), MAP2K1 (15q22.1-q22.33) and MAP2K2 (19p13.3) in acral lentiginous melanoma

Grant number: 12/11408-8
Support type:Regular Research Grants
Duration: February 01, 2013 - January 31, 2015
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal researcher:Gilles Landman
Grantee:Gilles Landman
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Janete Maria Cerutti

Abstract

Cutaneous melanoma is a malignant neoplasm arising from the uncontrolled proliferation of melanocytes skin. The acral lentiginous melanoma occurs in places not exposed to solar radiation, palms, soles and subungual areas, is more common in Asian and African descent, accounting for 2-3% of all melanoma cases. Studies that evaluate the signaling pathways in melanoma progression of this type contribute as prognostic indicators and therapeutic target. The MAP kinase pathway is responsible for signs of cell growth, differentiation and cell proliferation. The constitutive activation of this pathway is given by mutations on several levels. BRAF mutations appear preferentially in exons 11 and 15, the rate of 50 to 70%, being the most frequent mutation V600E, activating ERK. The MEK1 and MEK2 proteins are encoded by genes MAP2K and MAP2K2, appearing in 8% of melanomas. Mutations in these genes promote tumorigenesis, angiogenesis and progression of melanoma. Objective: To studyin acral lentiginous melanoma of the heterogeneity of mutations of the genes belonging to the MAP kinase pathway in different areas of the same tumor. Patients and Methods: Samples will be selected from patients who were diagnosed with acral lentiginous melanoma in the period 1996 to 2010, an estimated 50 cases, approximately. Mutations of the BRAF, MAP2K1 and MAP2K2 are analyzed by the sequencing and pyrosequencing, comparing the two methodologies. (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)
FERNANDES, MARIANA; BARCELOS, DENISE; COMODO, ANDREIA NEVES; GUIMARAES, DAIANE PEREIRA; LOPES CARAPETO, FERNANDO CINTRA; CARDILI, LEONARDO; MORAES, LAIS DE SOUSA; CERUTTI, JANETE; LANDMAN, GILLES. Acral Lentiginous Melanomas Harbour Intratumor Heterogeneity in BRAF Exon 15, With Mutations Distinct From V600E/V600K. AMERICAN JOURNAL OF DERMATOPATHOLOGY, v. 41, n. 10, p. 733-740, . (12/11408-8)

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