Topic
Suppressor mutation
About: Suppressor mutation is a research topic. Over the lifetime, 664 publications have been published within this topic receiving 27193 citations. The topic is also known as: Suppressor mutation.
Papers published on a yearly basis
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Papers
TL;DR: It is shown that loss of transactivation capacity is a key factor for the selection of missense mutations, and that difference in mutation frequencies is closely related to nucleotide substitution rates along TP53 coding sequence, which provides new insights into the factors that shape mutation patterns and influence mutation phenotype.
Abstract: The tumor suppressor gene TP53 is frequently mutated in human cancers More than 75% of all mutations are missense substitutions that have been extensively analyzed in various yeast and human cell assays The International Agency for Research on Cancer (IARC) TP53 database (www-p53iarcfr) compiles all genetic variations that have been reported in TP53 Here, we present recent database developments that include new annotations on the functional properties of mutant proteins, and we perform a systematic analysis of the database to determine the functional properties that contribute to the occurrence of mutational "hotspots" in different cancer types and to the phenotype of tumors This analysis showed that loss of transactivation capacity is a key factor for the selection of missense mutations, and that difference in mutation frequencies is closely related to nucleotide substitution rates along TP53 coding sequence An interesting new finding is that in patients with an inherited missense mutation, the age at onset of tumors was related to the functional severity of the mutation, mutations with total loss of transactivation activity being associated with earlier cancer onset compared to mutations that retain partial transactivation capacity Furthermore, 80% of the most common mutants show a capacity to exert dominant-negative effect (DNE) over wild-type p53, compared to only 45% of the less frequent mutants studied, suggesting that DNE may play a role in shaping mutation patterns These results provide new insights into the factors that shape mutation patterns and influence mutation phenotype, which may have clinical interest
1,730 citations
TL;DR: This work has shown that viral genetic diversity is determined by multiple virus- and host-dependent processes, and that viral mutation rates can evolve in response to specific selective pressures.
Abstract: The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair. Additionally, massive numbers of mutations can be introduced by some virus-encoded diversity-generating elements, as well as by host-encoded cytidine/adenine deaminases. Our current knowledge of viral mutation rates indicates that viral genetic diversity is determined by multiple virus- and host-dependent processes, and that viral mutation rates can evolve in response to specific selective pressures.
856 citations
TL;DR: This high-resolution mutation analysis allows evaluation of previous predictions and hypotheses through interrelation of function, structure and mutation in the tumor suppressor p53.
Abstract: Inactivation of the tumor suppressor p53 by missense mutations is the most frequent genetic alteration in human cancers. The common missense mutations in the TP53 gene disrupt the ability of p53 to bind to DNA and consequently to transactivate downstream genes. However, it is still not fully understood how a large number of the remaining mutations affect p53 structure and function. Here, we used a comprehensive site-directed mutagenesis technique and a yeast-based functional assay to construct, express, and evaluate 2,314 p53 mutants representing all possible amino acid substitutions caused by a point mutation throughout the protein (5.9 substitutions per residue), and correlated p53 function with structure- and tumor-derived mutations. This high-resolution mutation analysis allows evaluation of previous predictions and hypotheses through interrelation of function, structure and mutation.
852 citations
697 citations
TL;DR: It is shown that selection is more important than an increased mutation rate in the growth of a tumor, and some cancers may acquire a "mutator phenotype" leading to faster growth, but mutator phenotypes are not necessary for carcinogenesis.
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.
475 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2024 | 2 |
| 2023 | 2 |
| 2022 | 4 |
| 2021 | 4 |
| 2020 | 11 |
| 2019 | 9 |