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Analysis of Somatic Mutations in Cancer Tissues Challenges the Somatic Mutation Theory of Cancer

  1. Daniel Satgé

Published Online: 19 SEP 2013

DOI: 10.1002/9780470015902.a0024465

eLS

eLS

How to Cite

Satgé, D. 2013. Analysis of Somatic Mutations in Cancer Tissues Challenges the Somatic Mutation Theory of Cancer. eLS. .

Author Information

  1. University Institute for Clinical Research, Montpellier, France

Publication History

  1. Published Online: 19 SEP 2013

Abstract

According to the somatic mutation theory (SMT) of cancer, somatic mutations observed in cancerous tissues directly cause malignancy. However, a close look at the experimental data and observations about human diseases show many discrepancies with the theory, including the lack of specificity of the so-called ‘cancer genes’ that are mutated in noncancerous tissues, and not mutated in cancers; the rarity of malignancies in some genetic conditions with deoxyribonucleic acid repair anomalies and the high number of initial mutations in early carcinogenesis. Above all, abnormal proliferations and altered tissue architecture before specific genetic anomalies are detected strongly support the idea that the correlation between carcinogenesis and genetic modifications is more complex and probably less determining than has been theorised by the SMT. Other theories that take into account tissue architecture and microenvironment, such as the tissue organisation field theory, are promising paths towards an understanding of oncogenesis.

Key Concepts:

  • Initial somatic mutations are found in cancer tissues much more frequently than expected from a random event.

  • Proliferative and architectural anomalies are observed in organs before genetic anomalies occur.

  • Mutations of the so-called ‘cancer genes’ are present in noncancerous tissues.

  • Mutations of so-called ‘cancer genes’ are not present in all cells of a cancer/tumour.

  • Tissues maintain their respective phenotypes despite many mutations.

  • Some conditions with DNA repair deficiency have no increased risk of cancer, and some others appear to be protected against particular cancer types.

  • Cancers can be induced by transplanting a normal tissue into an unusual environment for that tissue.

  • Cancer cells can be reverted to normal cells when implanted into a microenvironment that is normal for this type of cells.

Keywords:

  • somatic mutation;
  • mutation rate;
  • carcinogenesis;
  • somatic mutation theory;
  • tissue organisation field theory;
  • oncogene;
  • tumour suppressor gene;
  • Down syndrome;
  • microenvironment