Related Experiment Video

Updated: Jul 13, 2026

Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model
09:03

Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model

Published on: October 16, 2017

Activation and transposition of endogenous retroviral elements in hypomethylation induced tumors in mice

G Howard1, R Eiges, F Gaudet

  • 1Department of Animal and Cell Biology, Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.

Oncogene
|July 11, 2007
PubMed

Insights

Genomewide DNA hypomethylation can cause tumors by increasing chromosomal instability and activating endogenous retroviruses like intracisternal A particles (IAPs). This study shows DNA hypomethylation

Area of Science:

  • Epigenetics and Cancer Research
  • Genomics and Molecular Biology
  • Tumorigenesis Mechanisms

Background:

  • Genomewide DNA hypomethylation is observed in human tumors, but its causal role in tumorigenesis is unclear.
  • Previous studies showed hypomethylation in Dnmt1(chip/-) mice leads to thymic lymphomas and chromosomal instability (trisomy 15).

Purpose of the Study:

  • To investigate the molecular mechanisms linking DNA hypomethylation to tumor development.
  • To identify specific genetic events contributing to lymphoma formation in hypomethylated mice.

Main Methods:

  • Analysis of lymphomas from mice with a hypomorphic DNA methyltransferase allele (Dnmt1(chip/-)).
  • Detection of somatic insertions within the Notch1 locus using genomic analysis.
  • Assessment of chromosomal instability in tumor cells.

Main Results:

  • Seven of 16 hypomethylation-induced lymphomas exhibited intracisternal A particle (IAP) insertions in the Notch1 gene.
  • These IAP insertions generated an oncogenic form of Notch1, contributing to tumor development.
  • Hypomethylation-induced tumors showed chromosomal instability, including trisomy 15.

Conclusions:

  • DNA hypomethylation promotes tumorigenesis through chromosomal instability and activation of endogenous retroelements like IAPs.
  • DNA methylation is crucial for suppressing transposable elements and maintaining normal cell function.
  • This study highlights the oncogenic potential of DNA hypomethylation and its link to retroviral element activation.

More Related Videos

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

Related Concept Videos

Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
Mouse Models of Cancer Study02:43

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.