Related Experiment Video

Updated: Nov 17, 2025

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis
09:45

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis

Published on: March 31, 2015

11.5K

Revertant somatic mosaicism as a cause of cancer

Toshiya Inaba1, Akiko Nagamachi1

  • 1Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.

Cancer Science
|February 14, 2021
PubMed

Insights

Revertant mosaicism, a natural gene correction, can paradoxically cause myelodysplastic syndrome and leukemia in SAMD9/9L syndromes through overcorrection. This study explores the complex mechanisms behind this "overcorrection" phenomenon in carcinogenesis.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Revertant mosaicism spontaneously corrects mutations, acting as 'natural gene therapy' for congenital diseases.
  • However, overcorrection in SAMD9/9L syndromes can induce myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML).

Purpose of the Study:

  • To interpret the complex mechanisms underlying MDS/AML development in SAMD9/9L syndromes due to revertant mosaicism.
  • To highlight overcorrection by somatic mosaicism as a novel mechanism in carcinogenesis.

Main Methods:

  • Review of existing literature on SAMD9/9L syndromes, revertant mosaicism, MDS, and AML.
  • Analysis of genetic and cellular mechanisms involving chromosome 7 tumor suppressors and interferon sensitivity.

Main Results:

  • Overcorrection by revertant mosaicism in SAMD9/9L syndromes leads to MDS with monosomy 7, potentially progressing to AML.
  • Mechanisms involve haploinsufficiency of multiple myeloid tumor suppressors on chromosome 7 and differential interferon sensitivity.

Conclusions:

  • Somatic mosaicism-induced overcorrection represents a novel pathway to carcinogenesis.
  • Understanding these mechanisms is crucial for managing SAMD9/9L syndromes and preventing hematologic malignancies.
Keywords:
SAMD9/9L syndromeshaploinsufficiencyrevertant mosaicismsomatic mutationtumor suppressors

More Related Videos

Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines07:49

Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines

Published on: March 17, 2023

2.9K
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

9.2K

Related Concept Videos

Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

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...
13.5K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.8K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.4K
Mismatch Repair01:20

Mismatch Repair

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...
5.8K
Mismatch Repair01:36

Mismatch Repair

Overview
42.7K
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...
5.8K