RESUMO
BACKGROUND: Activating RAS mutations in the germline cause rare developmental disorders such as Costello syndrome. Somatic RAS mutations are found in approximately 30% of human cancers. Keratinocytic epidermal nevi (KEN) represent benign congenital skin lesions arranged along Blaschko's lines. A subgroup of KEN is caused by hotspot oncogenic FGFR3 and PIK3CA mutations in mosaicism, but the majority lack these mutations. METHODS: This study screened 72 KEN for activating mutations in RAS genes and other oncogenes. RESULTS: Activating RAS mutations were identified in 28/72 (39%) of KEN. HRAS was the most commonly affected oncogene (86%), with the HRAS p.G13R substitution representing a new hotspot mutation. CONCLUSION: These results indicate that activating RAS somatic mutations leading to mosaicism result in benign KEN of the skin. Given the prevalence of KEN, mosaic HRAS mutations appear to be more common in patients than germline ones. These findings identify KEN as a mosaic RASopathy and lend further support to the notion that genetic mosaicism is an important contributor to disease.
Assuntos
Epiderme/patologia , Genes ras , Queratinócitos/patologia , Mosaicismo , Mutação , Nevo/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Fosfatidilinositol 3-Quinases/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Adulto JovemRESUMO
We have prepared the first platinum(II) metallosurfactants from a new family of linear surfactant phosphines Ph(2)P(CH(2))(n)SO(3)Na {1 (n = 2), 2 (n = 6), and 3 (n = 10)}, which were synthesized by reaction between the halosulfonates X(CH(2))(n)SO(3)Na and sodium diphenylphosphide. The metallosurfactants cis-[PtCl(2)L(2)] (L = 1-3) were obtained after reaction between the phosphines and PtCl(2) in dimethylsulfoxide. All compounds were fully characterized by the usual methods {NMR ((1)H, (13)C, (31)P, (195)Pt), IR, MS-ESI and HRMS}. By exploring the surfactant properties of phosphines 1-3 and their respective platinum metallosurfactants cis-[PtCl(2)L(2)] (L = 1-3) through surface tension measurements, dynamic light scattering spectroscopy, and cryo-TEM microscopy, we were able to analyze the influence of the metal coordination on the critical micelle concentration (cmc) and the aggregation properties. The cmc values of platinum metallosurfactants were considerably lower than those obtained for the free phosphines 1-3. This behavior could be understood by an analogy between the structure of cis-[PtCl(2)L(2)] complexes and bolaform surfactants. The calculated values of area per molecule also showed different tendencies between 1-3 and cis-[PtCl(2)L(2)] complexes, which could be explained on the basis of the possible conformations of these compounds in the air-water interface. The study of aggregates by dynamic light scattering spectroscopy and cryo-TEM microscopy showed the formation of spherical disperse medium size vesicles in all cases. However, substantial differences were observed between the three free phosphines (the population of micellar aggregates increased with long chain length) and also between phosphines and their respective metallosurfactants.
RESUMO
BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular lesions characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. Although often asymptomatic, seizures, cerebral haemorrhages and focal neurological deficits are well-documented complications. Mutations in the CCM1 (7q21-22), CCM2 (7p13-15) and CCM3 (3q25.2-27) genes have been identified in familial CCM. In rare instances, the association of congenital hyperkeratotic cutaneous capillary-venous malformations (HCCVMs) with CCM1 has been reported. OBSERVATIONS: We studied 6 members of a family with CCMs. Four members of the family developed late-onset multiple, tiny, bluish, soft, cutaneous papules, mainly located on the face, arm and abdominal area, corresponding histologically to venous malformations. A splice donor site mutation in intron 4 (c. 1146 + 1 G-->A) in the CCM1 gene was identified. CONCLUSIONS: Our findings suggest that mutations in the KRIT1 gene may cause phenotypically heterogeneous cutaneous vascular lesions other than those previously described as HCCVMs.
Assuntos
Neoplasias Encefálicas/genética , Malformações Vasculares do Sistema Nervoso Central/genética , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Proteínas Associadas aos Microtúbulos/genética , Mutação , Proteínas Proto-Oncogênicas/genética , Dermatopatias Vasculares/genética , Malformações Vasculares/genética , Adulto , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/complicações , Malformações Vasculares do Sistema Nervoso Central/complicações , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Humanos , Proteína KRIT1 , Masculino , Pessoa de Meia-Idade , Linhagem , Dermatopatias Vasculares/complicações , Dermatopatias Vasculares/patologia , Malformações Vasculares/complicações , Malformações Vasculares/patologia , Veias/anormalidadesAssuntos
Ácido Aminolevulínico/análogos & derivados , Nevo Sebáceo de Jadassohn/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Ácido Aminolevulínico/uso terapêutico , Nádegas , Humanos , Masculino , Pessoa de Meia-Idade , Nevo Sebáceo de Jadassohn/patologia , Resultado do TratamentoRESUMO
Metallo-vesicles are formed in water medium as a result of the supramolecular arrangement of molybdenum carbonyl metallosurfactants. These new kind of surfactants contain a hydrophobic metal carbonyl fragment and are easily prepared from surfactant phosphine ligands.