Related Experiment Video
Updated: Jul 2, 2026
08:16
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Subclonal phylogenetic structures in cancer revealed by ultra-deep sequencing
Peter J Campbell1, Erin D Pleasance, Philip J Stephens
1Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom.
Summary
Ultra-deep sequencing can track cancer
Area of Science:
- Genomics
- Cancer Biology
- Evolutionary Biology
Background:
- Cancer evolves through clonal expansion, acquiring somatic mutations.
- Tracking these mutations reveals cancer's evolutionary dynamics.
- Massively parallel sequencing can detect rare subclones.
Purpose of the Study:
- To investigate intraclonal diversification in B-cell chronic lymphocytic leukemia.
- To develop methods for detecting rare subclones and their phylogenetic relationships.
- To assess the utility of ultra-deep pyrosequencing in cancer evolution studies.
Main Methods:
- Ultra-deep pyrosequencing of the Ig heavy chain locus in 22 patients.
- Analysis of a control locus to identify sequencing artifacts.
- Development of an algorithm to distinguish genuine somatic hypermutations from artifacts.
Main Results:
- Sequencing artifacts were identified and differentiated from genuine mutations.
- A novel algorithm successfully detected rare subclones (frequency as low as 1 in 5000).
- Phylogenetic interrelationships among subclones within individual patients were characterized.
Conclusions:
- Ultra-deep resequencing is a powerful tool for studying cancer clonal evolution.
- This method allows for the detection and characterization of rare subclones.
- The findings have implications for understanding cancer dynamics and developing targeted therapies.
More Related Videos
15:07VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
10:27Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Related Concept Videos
02:54Evolutionary Relationships through Genome Comparisons
Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...
03:00Next-generation Sequencing
The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features.
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...
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...
01:05Cancer-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...
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...