Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Spontaneous and Induced Mutations01:30

Spontaneous and Induced Mutations

3.4K
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).
3.4K
Mismatch Repair01:20

Mismatch Repair

7.2K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
7.2K
Mismatch Repair01:36

Mismatch Repair

45.9K
Overview
45.9K
Mismatch Repair01:36

Mismatch Repair

13.3K
13.3K
Mutations01:39

Mutations

98.3K
Overview
98.3K
Mutations01:35

Mutations

46.5K
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...
46.5K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

A rare missense variant impacting NEK1 kinase function is associated with ALS.

Acta neuropathologica communications·2026
Same author

The spectrum of immunoglobulin heavy chain enhancer hijacking in chronic lymphocytic leukemia.

Leukemia·2026
Same author

Multi-layered molecular profiling informs the diagnosis and targeted therapy of desmoplastic small round cell tumor.

Nature communications·2026
Same author

Correction: RBM39 shapes innate immunity by controlling expression of key factors of the interferon response.

Frontiers in immunology·2026
Same author

A microenvironment-determined risk continuum refines subtyping in meningioma and reveals determinants of machine learning-based tumor classification.

Nature genetics·2026
Same author

Tissue-Based Multiomic Exploratory Analysis of the Urokinase Plasminogen Activator/uPAR System and Matrix Metalloproteinases in Stroma AReactive Invasion Front Areas-Positive Gastrointestinal Cancers.

Pathobiology : journal of immunopathology, molecular and cellular biology·2026

Related Experiment Video

Updated: Apr 15, 2026

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
09:35

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches

Published on: April 20, 2021

7.4K

Hypermutation takes the driver's seat.

Matthias Schlesner1, Roland Eils2

  • 1Division of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Heidelberg, 69120 Germany.

Genome Medicine
|March 31, 2015
PubMed
Summary
This summary is machine-generated.

Pediatric tumors with DNA mismatch repair deficiency show extremely high mutation rates. This is due to DNA polymerases compensating for the repair defect, driving tumor growth and offering new therapeutic targets.

More Related Videos

Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes
08:12

Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes

Published on: November 1, 2011

20.5K
Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
11:06

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells

Published on: February 24, 2014

13.6K

Related Experiment Videos

Last Updated: Apr 15, 2026

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
09:35

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches

Published on: April 20, 2021

7.4K
Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes
08:12

Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes

Published on: November 1, 2011

20.5K
Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
11:06

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells

Published on: February 24, 2014

13.6K

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Most pediatric tumors have a low mutational burden.
  • Congenital biallelic deficiency in DNA mismatch repair (MMR) is rare.

Purpose of the Study:

  • To investigate the mutational landscape of pediatric tumors with MMR deficiency.
  • To understand the mechanisms driving ultra-hypermutation in these tumors.
  • To explore therapeutic implications of these findings.

Main Methods:

  • Whole-exome sequencing of pediatric tumor samples.
  • Analysis of somatic mutation profiles.
  • Functional studies of DNA repair pathways.

Main Results:

  • A subset of pediatric tumors with MMR deficiency displayed an exceptionally high mutational load (ultra-hypermutation).
  • Somatic mutations in proofreading DNA polymerases were identified in these tumors.
  • These polymerase mutations were found to abolish replication repair, complementing the MMR deficiency.

Conclusions:

  • Ultra-hypermutation in pediatric tumors results from a combined defect in DNA mismatch repair and replication proofreading.
  • This unique mutational profile presents novel therapeutic opportunities for treating these aggressive cancers.