RESUMO
Loss of function mutations and deletions encompassing the plant homeodomain finger 6 (PHF6) gene are present in about 20% of T-cell acute lymphoblastic leukemias (ALLs). Here, we report the identification of recurrent mutations in PHF6 in 10/353 adult acute myeloid leukemias (AMLs). Genetic lesions in PHF6 found in AMLs are frameshift and nonsense mutations distributed through the gene or point mutations involving the second plant homeodomain (PHD)-like domain of the protein. As in the case of T-ALL, where PHF6 alterations are found almost exclusively in males, mutations in PHF6 were seven times more prevalent in males than in females with AML. Overall, these results identify PHF6 as a tumor suppressor gene mutated in AML and extend the role of this X-linked tumor suppressor gene in the pathogenesis of hematologic tumors.
Assuntos
Proteínas de Transporte/genética , Leucemia Mieloide Aguda/genética , Mutação , Adulto , Idoso , Animais , Feminino , Genes Supressores de Tumor , Células-Tronco Hematopoéticas/metabolismo , Humanos , Leucemia Mieloide Aguda/etiologia , Masculino , Camundongos , Pessoa de Meia-Idade , Células Mieloides/metabolismo , Proteínas Repressoras , Caracteres SexuaisRESUMO
A cellular automaton that is related to the "mosaic cycle concept" is considered. We explain why such automata sustain very often, but not always, n-periodic trajectories (n being the number of states of the automaton). Our work is a first step in the direction of a theory of these type of automata which might be useful in modeling mosaic successions.
Assuntos
Evolução Biológica , Ecossistema , Modelos Teóricos , Simulação por Computador , HumanosRESUMO
The evolution of DNA base composition evolution is simplified to a six-parameter model when there are no strand biases for mutation and selection. We analyzed the dynamics of this model with special attention to the influence of a change in substitution rates. The G + C content of the DNA sequence tends to an equilibrium value that is controlled by four parameters of the model. When the substitution rates are not constant, the G + C equilibrium position is not constant. The DNA sequence base frequencies always tend to a state in which A = T and G = C within a strand, regardless of substitution rates. This is true even when the substitution rates are not constant over time. This provides a simple way of rejecting the model from inspection of present-day DNA base composition.