The continuum model of selection in human tumors: general paradigm or niche product?

Cancer Research
Simon Leedham, Ian Tomlinson

Abstract

Berger and colleagues recently proposed a continuum model of how somatic mutations cause tumors to grow, thus supplementing the established binary models, such as oncogene activation and "two hits" at tumor suppressor loci. In the basic continuum model, decreases or increases in gene function, short of full inactivation or activation, impact linearly on cancer development. An extension, called the fail-safe model, envisaged an optimum level of gene derangement for tumor growth, but proposed that the cell gained protection from tumorigenesis because additional mutations caused excessive derangement. Most of the evidence in support of the continuum model came from Pten mutant mice rather than humans. In this article, we assess the validity and applicability of the continuum and fail-safe models. We suggest that the latter is of limited use: In part, it restates the existing "just right" of optimum intermediate gene derangement in tumorigenesis, and in part it is inherently implausible that a cell should avoid becoming cancerous only when it is some way down the road to that state. In contrast, the basic continuum model is a very useful addition to the other genetic models of tumorigenesis, especially in certain scenarios. Fitting...Continue Reading

References

Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A G Knudson
Oct 12, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M V Blagosklonny
Aug 2, 2005·Nature Reviews. Cancer·Oliver M SieberIan P M Tomlinson
Jun 20, 2006·Genetics·Chris GreenmanDouglas F Easton
May 24, 1974·Science·D D Jones
Apr 27, 2010·Current Opinion in Genetics & Development·Jajini Susan Varghese, Douglas F Easton
Aug 13, 2011·Nature·Alice H BergerPier Paolo Pandolfi

❮ Previous
Next ❯

Citations

Sep 13, 2005·Cancer Cell International·Toni M RichterSteven B Scholnick
Oct 9, 2014·Annual Review of Genetics·Marco GerlingerCharles Swanton
Jun 14, 2014·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Paul LochheadShuji Ogino
Jul 18, 2017·Nature Methods·Eduard Porta-PardoAdam Godzik
Apr 30, 2019·PLoS Computational Biology·Anna-Leigh BrownAnna R Panchenko
Jul 25, 2018·International Journal of Molecular Sciences·Feiyang ZhaoMinghui Li

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.