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    • "Histologically, melanocytes are completely absent in the white spot area due to defective melanoblasts proliferation and/or migration from the neural crest during early embryonic development [5]. Because of its distinctive phenotype, the first descriptions of piebaldism date back to early Egyptian, Greek and Roman writings [3] [5]. It was one of the first autosomal dominant genetic disorders recognized and was also one of the first genetic diseases for which a pedigree was presented. "
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    ABSTRACT: The present study is aimed at performing the molecular characterization of a Tunisian family with piebaldism. As the proband and her mother showed a severe phenotype, we first chose to screen exons 10, 11, 12, 13, 16, 17 and 18 of the KIT proto-oncogene by direct sequencing. Direct sequencing analysis showed a C to T substitution at 1939 in exon 13 (c.1939C>T) in heterozygous state in the patient and his mother. The mutation was not found in their unaffected family members or normal controls. Our results provide additional support that mutations in the tyrosine kinase domain of the KIT gene are responsible for the severe form of piebaldism. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    Pathologie Biologie 04/2015; 63(3). DOI:10.1016/j.patbio.2015.03.004 · 1.07 Impact Factor
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    • "MITF dysfunction is implicated in several genetic diseases such as Waardenburg syndrome type 2 (Tassabehji et al., 1994), Tietz syndrome (Smith et al., 2000), albinism-deafness syndrome (Amiel et al., 1998), osteopetrosis and pycnodysostosis (Motyckova et al., 2001). MITF is indirectly implicated in the Griscelli syndrome (Van Gele et al., 2009) and piebaldism (Thomas et al., 2004); low expression of MITF in the former disease can be caused by mutations in the upstream KIT gene, and in the later it can downregulate its target gene (RAB27A), which is essential for normal pigmentation . Mice lacking MITF have abnormally small eyes, a white coat and developmental defects in mast cells and osteoclasts (Steingrímsson et al., 2004). "
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    ABSTRACT: Studies examining intratumor heterogeneity have indicated that several cancer types, including melanoma, can display phenotypic plasticity, corresponding to their capacity to undergo transient reversible cellular changes. Conceptual models constructed to explain the process of cancer propagation differ in their treatment of intratumor heterogeneity. Recent observations of reversible phenotypic heterogeneity in melanoma have led to the proposal of a novel 'phenotypic plasticity' model of cancer propagation. Microphthalmia-associated transcription factor (MITF), the melanocyte 'lineage-specific' transcription factor, has emerged as one of the central players in melanoma phenotypic plasticity. Here we discuss the conceptual models suggested to explain the relations between MITF and melanoma plasticity, in addition to the complex regulatory roles that MITF plays in melanocytes and melanoma development. Finally, we provide an in-depth literature survey of microRNAs (miRNAs) involved in MITF activity, melanoma propagation and metastasis, in addition to their potential use as agents of personalized therapy.
    Pigment Cell & Melanoma Research 12/2011; 24(6):1088-106. DOI:10.1111/j.1755-148X.2011.00931.x · 5.64 Impact Factor
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    ABSTRACT: CD117 (KIT) is a type III receptor tyrosine kinase operating in cell signal transduction in several cell types. Normally KIT is activated (phosphorylated) by binding of its ligand, the stem cell factor. This leads to a phosphorylation cascade ultimately activating various transcription factors in different cell types. Such activation regulates apoptosis, cell differentiation, proliferation, chemotaxis, and cell adhesion. KIT-dependent cell types include mast cells, some hematopoietic stem cells, germ cells, melanocytes, and Cajal cells of the gastrointestinal tract, and neoplasms of these cells are examples of KIT-positive tumors. Other KIT-positive normal cells include epithelial cells in skin adnexa, breast, and subsets of cerebellar neurons. KIT positivity has been variably reported in sarcomas such as angiosarcoma, Ewing sarcoma, synovial sarcoma, leiomyosarcoma, and MFH; results of the last three are controversial. The variations in published data may result from incomplete specificity of some polyclonal antibodies, possibly contributed by too high dilutions. Also, KIT is expressed in pulmonary and other small cell carcinomas, adenoid cystic carcinoma, renal chromophobe carcinoma, thymic, and some ovarian and few breast carcinomas. A good KIT antibody reacts with known KIT positive cells, and smooth muscle cells and fibroblasts are negative. KIT deficiency due to hereditary nonsense/missense mutations leads to disruption of KIT-dependent functions such as erythropoiesis, skin pigmentation, fertility, and gastrointestinal motility. Conversely, pathologic activation of KIT through gain-of-function mutations leads to neoplasia of KIT-dependent and KIT-positive cell types at least in three different systems: mast cells/myeloid cells--mastocytosis/acute myeloid leukemia, germ cells--seminoma, and Cajal cells--gastrointestinal stromal tumors (GISTs). KIT tyrosine kinase inhibitors such as imatinib mesylate are the generally accepted treatment of metastatic GISTs, and their availability has prompted an active search for other treatment targets among KIT-positive tumors such as myeloid leukemias and small cell carcinoma of the lung, with variable and often nonconvincing results.
    Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 10/2005; 13(3):205-20. DOI:10.1097/01.pai.0000173054.83414.22 · 2.06 Impact Factor
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