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Genetic Mosaicism and Cancer: Cause and Effect.
1Institute of Carcinogenesis, N.N. Blokhin Cancer Research Center, Moscow, Russia. alicht@mail.ru.
Cancer Research
|February 24, 2018
Summary
Cellular genomes continuously change due to replication errors, mitosis defects, and oxidative stress, leading to somatic mosaicism. This genetic diversity suggests the microenvironment, or "soil," generates and supports cancer development.
Area of Science:
- Genetics
- Cell Biology
- Cancer Research
Background:
- Genomic instability is increasingly recognized in normal and cancer cells.
- Sources of genomic changes include replication errors, chromosome segregation defects, and reactive oxygen species.
- Cellular genetic diversification begins during development and continues throughout life, resulting in somatic mosaicism.
Purpose of the Study:
- To reconsider existing concepts of cancer etiology and pathogenesis in light of cellular genetic diversity.
- To propose a new model for cancer development focusing on the microenvironment.
Main Methods:
- Review of theoretical and experimental evidence on genomic instability.
- Conceptual synthesis of genetic diversification and cancer development.
Main Results:
- Genomes are subject to continuous changes throughout life.
- Somatic mosaicism is a widespread phenomenon.
- The concept of a deteriorating microenvironment generating cancer is proposed.
Conclusions:
- Genetic diversity of somatic cells necessitates a re-evaluation of cancer etiology.
- The tumor microenvironment (
- soil
- ) plays a critical role in cancer initiation and progression.
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