JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Somatic Mutations in DNA Mismatch Repair Genes, Mutation Rate and Neoantigen Load in Acute Lymphoblastic Leukemia

  • 0Laboratorio de Innovación y Medicina de Precisión, Núcleo A, Instituto Nacional de Medicina Genómica, Ciudad de Mexico 14610, Mexico.
Pharmaceuticals (basel, Switzerland) +

|

September 27, 2025

|

September 27, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Researchers identified potential neoantigens in pediatric acute lymphoblastic leukemia (ALL). These findings support neoantigen-based immunotherapy as a promising treatment, particularly for relapsed ALL patients.

Area Of Science

  • Oncology
  • Immunology
  • Genetics

Background

  • Tumor cells acquire somatic mutations, potentially creating tumor-specific neoantigens recognized by the immune system.
  • Pediatric cancers, like acute lymphoblastic leukemia (ALL), generally have fewer mutations and neoantigens compared to adult tumors.
  • Understanding the neoantigen landscape in pediatric ALL is crucial for developing novel immunotherapy strategies.

Purpose Of The Study

  • To identify potential neoantigens in pediatric acute lymphoblastic leukemia (ALL) patients.
  • To investigate the relationship between tumor mutational burden (TMB), neoantigen load, and clinical outcomes in pediatric ALL.

Main Methods

  • Whole-exome sequencing of matched tumor-normal samples from pediatric ALL cases.
  • Prediction of HLA-I alleles and identification of somatic mutations.
  • Proposal of potential neoantigens based on mutated peptide-HLA-I binding affinity.

Main Results

  • A significant correlation was observed between tumor mutational burden (TMB) and neoantigen load (p < 0.001).
  • TMB and neoantigen levels were higher in ALL patients with mutated DNA mismatch repair genes (p < 0.001).
  • No significant correlation was found between TMB/neoantigen load and patient prognosis.

Conclusions

  • The identification of neoantigens in pediatric ALL supports neoantigen-based immunotherapy as a viable treatment strategy.
  • This approach shows particular promise for treating pediatric ALL patients experiencing relapse.
  • Further research into neoantigen landscapes can advance personalized cancer treatments.

Keywords:

Related Concept Videos

Mismatch Repair 01:20

6.3K

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...

Mismatch Repair 01:36

43.5K

Overview

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...

Cancers Originate from Somatic Mutations in a Single Cell 02:21

14.6K

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...

Nucleotide Excision Repair 01:38

5.0K

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...

Nucleotide Excision Repair 01:08

40.6K

Overview

Exposure to mutagens can damage DNA and result in bulky lesions that distort the double-helix structure or impede proper transcription. Damaged DNA can be detected and repaired in a process called nucleotide excision repair (NER). NER employs a set of specialized proteins that first scan DNA to detect a damaged region. Next, NER proteins separate the strands and excise the damaged area. Finally, they coordinate the replacement with new, matching nucleotides.

DNA distortion and damage

Spontaneous and Induced Mutations 01:30

2.1K

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).