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    Avaliação da heterogeneidade intratumoral e intermetástases do éxon 15 do gene braf (7q34) em amostras de melanoma metastático
    (Universidade Federal de São Paulo (UNIFESP), 2015-06-05) Guimaraes, Daiane Pereira [UNIFESP]; Landman, Gilles Landman [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Approximately a half of cutaneous melanoma has a BRAF V600E mutation and benefits from treatment with BRAF and MEK inhibitors, showing rapid tumor regression. However, most of these patients had progression of disease within 6 to 12 months after initiation of treatment. The intratumoral heterogeneity has been demonstrated and may contribute to the failure to treatment and drug resistance and may have important consequences to personalized cancer therapy Objective: To study the heterogeneity of mutations in genes belonging to the MAPK pathway in metastatic melanoma, in different areas of the same tumor and among tumors of the same patient. Methods: Analysis of mutations in exon 15 of BRAF, by Sanger sequencing, in metastatic melanoma paraffin samples stored in the Department of Pathology, from 1996 to 2012. Results: 86 samples of metastatic melanoma were analyzed from 54 patients. 17 (31.5%) patients had at least one mutation in exon 15 and ten patients (18.5%) had V600E mutation. 22.2% (12) of the cases, at least one sample presented intratumoral heterogeneity related to the expression of exon 15. When just codon V600 was observed, 7 (13%) patients had at least one sample with intratumoral heterogeneity related to V600E mutation. Twelve (22.2%) patients had at least two samples of metastasis and among them, nine (75%) was exon 15 mutaded and all of them presented both intratumoral and intermetastatic heterogeneity. Conclusion: Intratumoral and intermetastatic heterogeneity of the expression of exon 15 of BRAF was observed in metastatic melanoma samples.