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1.
Gynecol Oncol ; 134(1): 10-4, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24802725

RESUMEN

OBJECTIVE: The aim of this study was to evaluate a series of primary melanomas of the female urogenital tract for oncogenic mutations in KIT, NRAS and BRAF in order to identify patients who may be amenable to targeted therapy. METHODS: We reviewed twenty-four cases of female urogenital tract melanomas and used Sanger sequencing analysis for the detection of oncogenic mutations in exons 9, 11, 13, and 17 of KIT; exons 2 and 3 of NRAS; and exon 15 of BRAF. RESULTS: Twenty-four patients were included: fourteen vaginal melanomas, four cervical melanomas, five urethral melanomas and one vulvar melanoma. NRAS mutations (4/24, 21%) were more prevalent than KIT mutations (1/24, 4%), while BRAF mutations were absent. Three of four NRAS mutations were present in vaginal melanomas (21%), mainly affecting codon 61 (3/4). They were mutually exclusive with the KIT mutation. The KIT mutation was present in a vaginal melanoma and affected exon 17. CONCLUSIONS: Melanomas of the female urogenital tract relatively commonly harbor mutations in NRAS; this makes NRAS an interesting therapeutic target for these patients in the advanced setting. KIT mutations were rare in our study in contrast to some previous reports. We cannot exclude that anatomical site-related differences and/or population related differences in KIT mutation frequency exist within urogenital tract melanomas.


Asunto(s)
GTP Fosfohidrolasas/genética , Neoplasias de los Genitales Femeninos/genética , Melanoma/genética , Proteínas de la Membrana/genética , Mutación , Neoplasias Ureterales/genética , Adulto , Anciano , Anciano de 80 o más Años , Exones , Femenino , Formaldehído , Neoplasias de los Genitales Femeninos/enzimología , Neoplasias de los Genitales Femeninos/epidemiología , Humanos , Sistema de Señalización de MAP Quinasas , Melanoma/enzimología , Melanoma/epidemiología , Persona de Mediana Edad , Epidemiología Molecular , Países Bajos/epidemiología , Adhesión en Parafina , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-kit/genética , Estudios Retrospectivos , Fijación del Tejido
2.
Behav Brain Res ; 265: 111-20, 2014 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-24556203

RESUMEN

Mouse gene Ptprr encodes multiple protein tyrosine phosphatase receptor type R (PTPRR) isoforms that negatively regulate mitogen-activated protein kinase (MAPK) signaling pathways. In the mouse brain, PTPRR proteins are expressed in cerebellum, olfactory bulb, hippocampus, amygdala and perirhinal cortex but their precise role in these regions remains to be determined. Here, we evaluated phenotypic consequences of loss of PTPRR activity and found that basal smell was normal for Ptprr(-/-) mice. Also, spatial learning and fear-associated contextual learning were unaffected. PTPRR deficiency, however, resulted in impaired novel object recognition and a striking increase in exploratory activity in a new environment. The data corroborate the importance of proper control of MAPK signaling in cerebral functions and put forward PTPRR as a novel target to modulate synaptic processes.


Asunto(s)
Condicionamiento Clásico/fisiología , Conducta Exploratoria/fisiología , Trastornos de la Memoria/genética , Proteínas Tirosina Fosfatasas Clase 7 Similares a Receptores/deficiencia , Reconocimiento en Psicología/fisiología , Análisis de Varianza , Animales , Extinción Psicológica , Miedo/fisiología , Femenino , Masculino , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Tirosina Fosfatasas Clase 7 Similares a Receptores/genética , Olfato/genética , Factores de Tiempo
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