Video Experimental Relacionado

Updated: Nov 9, 2025

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Published on: November 5, 2019

Caracterización de la heterogeneidad genética intra-tumoral en 2.658 genomas de cáncer humano

Stefan C Dentro¹, Ignaty Leshchiner², Kerstin Haase³

¹Cancer Genomics Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK; Big Data Institute, University of Oxford, Oxford OX3 7LF, UK.

|April 8, 2021

Resumen

La heterogeneidad intra-tumoral (ITH) impulsa la resistencia terapéutica. Este estudio analiza 2.658 secuencias de genoma completo en 38 tipos de cáncer, revelando expansiones subclonales generalizadas y mutaciones impulsoras cruciales para comprender la evolución del tumor.

Área de la Ciencia:

La genómica
Biología del cáncer
La medicina evolutiva

Sus antecedentes:

La heterogeneidad intra-tumoral (ITH) es un mecanismo clave de resistencia terapéutica y un desafío clínico significativo.
La extensión completa, los orígenes y los impulsores de la ITH en diversos tipos de cáncer siguen siendo poco conocidos.
La caracterización de la ITH es crucial para desarrollar tratamientos más efectivos contra el cáncer.

Objetivo del estudio:

Caracterizar exhaustivamente la ITH en una gran cohorte de cáncer de páncreas utilizando la secuenciación de todo el genoma.
Identificar el alcance y los patrones de expansión subclonal y sus relaciones evolutivas.
Investigar los factores y procesos mutacionales que contribuyen a la ITH en varios tipos de cáncer.

Principales métodos:

Secuenciación del genoma completo (WGS) de 2.658 muestras de cáncer de 38 tipos distintos de cáncer.
Análisis bioinformático para identificar poblaciones subclonales distintas y sus relaciones filogenéticas.
Análisis en profundidad de las alteraciones genéticas, incluidas las mutaciones impulsoras, las fusiones de genes, las variantes estructurales y las alteraciones del número de copias dentro de los subclones.

Principales resultados:

Se encontraron evidencias de expansiones subclonales distintas en el 95,1% de las muestras informativas, a menudo con patrones de ramificación complejos.
Se observó una selección positiva de mutaciones subclonales en la mayoría de los tipos de cáncer analizados.
Se identificaron patrones específicos del tipo de cáncer de alteraciones genéticas subclonales y cambios dinámicos en los procesos mutacionales.

Conclusiones:

La ITH es una característica generalizada del cáncer, caracterizada por expansiones subclonales generalizadas y eventos impulsores.
Comprender la arquitectura subclonal y la dinámica evolutiva es fundamental para la progresión del cáncer y la resistencia terapéutica.
Este estudio proporciona un valioso recurso pan-cancerígeno para la anotación de eventos subclonales a partir de datos WGS, ayudando a futuras investigaciones y aplicaciones clínicas.

Palabras clave:

Evolución de las ramas genes impulsores del cáncer Evolución del cáncer Heterogeneidad intra-tumoral genómica del cáncer reconstrucción subclonal Filogenia del tumor secuenciación del genoma completo

Más Videos Relacionados

Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence

Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence

Published on: October 25, 2011

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers

Published on: December 5, 2017

Videos de Conceptos Relacionados

Cancers Originate from Somatic Mutations in a Single Cell

Cancers 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...

Cancer-Critical Genes II: Tumor Suppressor Genes

Cancer-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...

Adaptive Mechanisms in Cancer Cells

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

Genetic Variation

Genetic Variation

Genetic variation is the diversity in DNA sequences found among individuals of the same species. This diversity is crucial for a species' survival because it helps organisms adapt to environmental changes. Genetic variation begins with fertilization, where an egg and sperm cell merge. Each of these cells carries 23 chromosomes, up to 46 in the fertilized egg. Chromosomes are long DNA strands that contain genes, the basic units of heredity.
Genes exist in different versions called alleles,...

Tumor Progression

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...

Cancer

Cancer

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.