The mutation rate and cancer

Abstract

The selection of advantageous mutations underlies tumorigenesis. The growth of a tumor is therefore a form of evolution at the somatic level, in which the population is comprised of individual cells within the tumor. Models of tumorigenesis have considered the relative importance of mutation and selection. We show that selection is more important than an increased mutation rate in the growth of a tumor. Some cancers may acquire a ''mutator phenotype,'' probably leading to faster growth, but mutator phenotypes are not necessary for carcinogenesis.

Adaptive dynamics of unstable cancer populations: The canonical equation

“…The number of both oncogenes and house‐keeping genes have been widely assessed, and we take them to be about $N_R\approx 140$ (Vogelstein et al., 2013) and $N_{\mathrm{normalHK}}\approx 3804$ (Eisenberg & Levanon, 2013), respectively. Interestingly enough, considering small replication effects for ${\mathrm{\delta }}_R$, such experimental values produce an adaptive landscape (Figure 2) that has a positive gradient within the region of $\mathrm{\mu }\in [{10}^{-9},{10}^{-4}]$, so that our evolutionary trajectories will be bounded within a region of instability levels in accordance with those experimentally measured for tumour cells (Tomlinson, Novelli, & Bodmer, 1996). …”

Methylation reveals a niche: stem cell succession in human colon crypts

“…Mutations rarely occur in normal cells and the probability that a single cell will accumulate multiple mutations is extremely low (Loeb, 1991). However, like the clonal succession of tumor progression, which increases the probability of further hits because more cells are at risk (Tomlinson et al, 1996), alteration followed by niche succession may also expedite further progression because multiple stem cells are present in a niche. A 'consensus' tag is 10100111 for crypt 1 and 00001000 for crypt 2.…”

Aneuploidy and Cancer: From Correlation to Causation

“…And phenotypic variation of normal cells by conventional gene mutation cells is limited to 10 Ϫ7 per cell generation for dominant genes and to 10 Ϫ14 for pairs of recessive genes in all species [6,47,52,57,68,69]. Even the mutation rates of most cancers are not higher than those of normal cells [6,19,20,47,66,[70][71][72][73][74][75]. Thus, phenotypic variation in cancer cells can be four to eleven orders faster than conventional mutation.…”

“…Examples are the 'high rates', compared to mutation, at which some cancers generate metastatic cells [59,60], or generate drug-resistant variants [53,54,56,58]. But the mutation rates of most cancers are not higher than those of normal cells [6,19,20,47,66,[70][71][72][73][74]. 6 Heritable Cancer Genes, but no Heritable Cancer.…”