Regulación dinámica de DNA extracromosomal

Interesante artículo. ¿Cual será el mecanismo para producir estos fragmentos extracromosomales? La creación  de cromosomas doble minuta y selección? Sin embargo habría que explicar como a partir de una célula se puede reproducir la población (debería ser un mecanismo rápido y lo suficientemente importante para seleccionarse).

Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA Science 3 January 2014: Vol. 343 no. 6166 pp. 72-76

Intratumoral heterogeneity contributes to cancer drug resistance, but the underlying mechanisms are not understood. Single-cell analyses of patient-derived models and clinical samples from glioblastoma patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) demonstrate that tumor cells reversibly up-regulate or suppress mutant EGFR expression, conferring distinct cellular phenotypes to reach an optimal equilibrium for growth. Resistance to EGFR TKIs is shown to occur by elimination of mutant EGFR from extrachromosomal DNA. After drug withdrawal, reemergence of clonal EGFR mutations on extrachromosomal DNA follows. These results indicate a highly specific, dynamic, and adaptive route by which cancers can evade therapies that target oncogenes maintained on extrachromosomal DNA.


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