Video Experimental Relacionado
Updated: May 8, 2026
11:15
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
El panorama en expansión de las mutaciones "oncohistónicas" en los cánceres humanos
Benjamin A Nacev1,2, Lijuan Feng2, John D Bagert3
1Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|March 22, 2019
Resumen
Las mutaciones histónicas somáticas se encuentran en aproximadamente el 4% de diversos cánceres, afectando regiones proteicas cruciales. Estas mutaciones en las histonas centrales pueden conducir al cáncer al alterar la función de la cromatina.
Área de la Ciencia:
- Biología del cáncer
- La epigenética
- Biología molecular
Sus antecedentes:
- Las mutaciones en las vías epigenéticas son factores clave del cáncer.
- Las mutaciones de la histona, en particular las "oncohistonas" en las colas N-terminales de la histona H3, son conocidas en cánceres específicos y afectan a los complejos represores policombos (PRC1 y PRC2).
- La prevalencia más amplia y el impacto funcional de las mutaciones histónicas en varios tipos de cáncer siguen siendo en gran medida inexploradas.
Objetivo del estudio:
- Investigar la prevalencia y localización de mutaciones histónicas somáticas en una amplia gama de tumores humanos.
- Identificar las regiones críticas de histonas y los residuos afectados por mutaciones.
- Para formular la hipótesis de las consecuencias funcionales de estas mutaciones en la regulación de la cromatina y el desarrollo del cáncer.
Principales métodos:
- Análisis de un conjunto de datos completo de mutaciones de histonas somáticas en varios tipos de tumores.
- Identificación de las ubicaciones de la mutación dentro de las proteínas histónicas, incluidas las colas N-terminales y los dominios globulares.
- Comparación de las mutaciones identificadas con los dominios funcionales conocidos y los mutantes de levadura homólogos.
Principales resultados:
- Se identificaron mutaciones histónicas somáticas en aproximadamente el 4% de los diversos tumores.
- Las mutaciones afectan a las cuatro histonas centrales (H2A, H2B, H3, H4) tanto en las colas N-terminales como en los dominios globulares.
- Las mutaciones ocurren cerca de los sitios clave de modificación post-traducional, en el parche ácido de H2A/H2B, y en la interfaz H2B-H4, con algunos mutantes homólogos a la levadura que afectan la función SWI/SNF.
Conclusiones:
- Las mutaciones histónicas somáticas son más frecuentes y diversas de lo que se reconocía anteriormente.
- Estas mutaciones ocurren en regiones funcionalmente críticas de las histonas, lo que sugiere un papel significativo en la oncogénesis.
- Los hallazgos proporcionan un recurso valioso para futuras investigaciones sobre el papel de las mutaciones histónicas en el cáncer y la regulación de la cromatina.
Videos de Conceptos Relacionados
02:18Cancer
Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
01:33Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
01:33Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...