Related Experiment Video
Updated: Feb 9, 2026
15:05
Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
9.3K
Molecular profiling and sequential somatic mutation shift in hypermutator tumours harbouring POLE mutations
Keiichi Hatakeyama1, Keiichi Ohshima2, Takeshi Nagashima3,4
1Medical Genetics Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka, 411-8777, Japan. k.hatakeyama@scchr.jp.
Scientific Reports
|June 9, 2018
Summary
Defective DNA polymerase ε (POLE) proofreading causes significant tumor mutations. PTEN mutations appear crucial for POLE-mutated tumor development and restore homologous recombination.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Defective DNA polymerase ε (POLE) proofreading is linked to extensive, biased somatic mutations in tumors.
- The specific molecular characteristics and mutational patterns of POLE-mutated tumors are not well understood.
Purpose of the Study:
- To elucidate the molecular profile and mutational patterns of POLE-mutated solid tumors.
- To identify key genetic events and their temporal order in the development of POLE-mutated tumors.
Main Methods:
- Whole exome sequencing of 10 POLE-mutated solid tumors from 2,042 Japanese patients.
- Quantification and classification of somatic mutation accumulation patterns into three sequential periods.
Main Results:
- Identified a distinct mutational signature associated with POLE defects.
- Observed PTEN mutations occurring concurrently with or subsequent to POLE defects, implicating both in tumorigenesis.
- Demonstrated restoration of homologous recombination following PTEN mutations.
Conclusions:
- POLE and PTEN mutations are key drivers in the development of POLE-mutated tumors.
- The study provides a framework for understanding mutation-driven tumorigenesis through somatic mutation footprint analysis.
Related Concept Videos
01:39Mutations
94.6K
Overview
94.6K
01:35Mutations
44.6K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.6K
00:36Viral Mutations
39.9K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
39.9K
02:21Cancers Originate from Somatic Mutations in a Single Cell
14.9K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
14.9K
01:09Mutation, Gene Flow, and Genetic Drift
64.5K
In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
64.5K
01:30Point and Frameshift Mutations
1.2K
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
1.2K