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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...

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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...

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Related Experiment Video

Updated: Jul 9, 2026

Characterizing Mutational Load and Clonal Composition of Human Blood

Characterizing Mutational Load and Clonal Composition of Human Blood

Published on: July 11, 2019

The evolution of two mutations during clonal expansion.

Hiroshi Haeno¹, Yoh Iwasa, Franziska Michor

¹Department of Biology, Kyushu University, Fukuoka, Japan.

|December 13, 2007

Summary

This summary is machine-generated.

Knudson's two-hit hypothesis explains retinoblastoma by requiring two genetic mutations. This study models how cell populations acquire these mutations during growth, impacting cancer development and treatment resistance.

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Published on: December 28, 2015

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Last Updated: Jul 9, 2026

Characterizing Mutational Load and Clonal Composition of Human Blood

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Published on: July 11, 2019

Following the Dynamics of Structural Variants in Experimentally Evolved Populations

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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma

VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma

Published on: December 28, 2015

Area of Science:

Genetics
Cancer Biology
Evolutionary Biology

Background:

Knudson's two-hit hypothesis posits two RB1 gene mutations drive retinoblastoma.
Inherited retinoblastoma requires one mutation at birth; sporadic cases accumulate two mutations.
Two-mutation events are crucial in cancer progression, drug resistance, and metastasis.

Purpose of the Study:

To model the probability of acquiring two critical mutations in an exponentially growing cell population.
To analyze the dynamics of clonal expansion and mutation accumulation.
To provide a theoretical framework for understanding multi-step carcinogenesis and treatment evasion.

Main Methods:

Mathematical modeling of cell populations with varying mutation statuses.
Calculation of mutation acquisition probabilities based on mutation rates and cell kinetics.
Development of a formula for the expected number of double-mutant cells at a given population size.

Main Results:

The probability of evolving two mutations depends on mutation rates, cell growth/death rates, and final population size.
A formula was derived to predict the number of cells with both mutations at population's end.
The study quantifies the dynamics of two-mutation evolution during clonal expansion.

Conclusions:

The theoretical model provides insights into the kinetics of acquiring two rate-limiting mutations.
This framework is applicable to retinoblastoma, cancer evolution, and drug resistance.
Understanding these dynamics is key to predicting disease progression and therapeutic outcomes.