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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...

Mutations

Mutations

Spontaneous and Induced Mutations

Spontaneous and Induced Mutations

Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).

Mismatch Repair

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...

Mismatch Repair

Mismatch Repair

Mutations in Microorganisms

Mutations in Microorganisms

Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...

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Related Experiment Video

Updated: Nov 7, 2025

Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing

Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing

Published on: October 18, 2013

Somatic mutation landscapes at single-molecule resolution.

Federico Abascal¹, Luke M R Harvey¹, Emily Mitchell^1,2

¹Wellcome Sanger Institute, Hinxton, UK.

|April 29, 2021

Summary

This summary is machine-generated.

Somatic mutations, DNA changes in cells, are key to cancer and aging. New nanorate sequencing (NanoSeq) allows detection of these mutations in single cells, revealing insights into tissue mutagenesis.

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Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay

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Published on: August 14, 2018

Single Cell Analysis Of Transcriptionally Active Alleles By Single Molecule FISH

Single Cell Analysis Of Transcriptionally Active Alleles By Single Molecule FISH

Published on: September 20, 2020

Related Experiment Videos

Last Updated: Nov 7, 2025

Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing

Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing

Published on: October 18, 2013

Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay

Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay

Published on: August 14, 2018

Single Cell Analysis Of Transcriptionally Active Alleles By Single Molecule FISH

Single Cell Analysis Of Transcriptionally Active Alleles By Single Molecule FISH

Published on: September 20, 2020

Area of Science:

Genetics
Molecular Biology
Cancer Research

Background:

Somatic mutations are crucial in cancer, aging, and disease development.
Detecting low-frequency somatic mutations in single cells has been a significant challenge, limiting studies to specific tissues.
Understanding somatic mutagenesis across diverse cell types and conditions is essential.

Purpose of the Study:

To develop a highly sensitive sequencing method for detecting low-frequency somatic mutations.
To investigate somatic mutation loads and signatures in various tissues, including non-dividing cells.
To compare mutagenesis in dividing versus non-dividing cells and stem versus differentiated cells.

Main Methods:

Development of nanorate sequencing (NanoSeq), a duplex sequencing protocol.
Achieving ultra-low error rates (<5 errors/billion base pairs) at the single-molecule level.
Application of NanoSeq to study somatic mutations in stem cells, differentiated cells, neurons, and smooth muscle.

Main Results:

NanoSeq enables the study of somatic mutations in any tissue, independent of clonality.
Differentiated blood and colon cells show similar mutation loads and signatures to stem cells, irrespective of cell division history.
Post-mitotic neurons and smooth muscle cells accumulate somatic mutations at a constant rate throughout life, comparable to mitotically active tissues.

Conclusions:

Cell division is not the sole driver of somatic mutagenesis; non-division-dependent processes are significant contributors.
Somatic mutations accumulate constantly in non-dividing cells like neurons.
The ability to detect single-molecule DNA mutations can revolutionize the study of somatic mutagenesis and enable large-scale, non-invasive cohort studies.