Related Experiment Video

Updated: Oct 6, 2025

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
12:04

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells

Published on: March 10, 2023

3.9K

How can same-gene mutations promote both cancer and developmental disorders?

Ruth Nussinov1,2, Chung-Jung Tsai1, Hyunbum Jang1

  • 1Computational Structural Biology Section, Frederick National Laboratory for Cancer Research in the Laboratory of Cancer Immunometabolism, National Cancer Institute, Frederick, MD 21702, USA.

Science Advances
|January 14, 2022
PubMed

Insights

Same gene mutations can cause both cancer and neurodevelopmental disorders. Cell type, timing, and mutation dosage explain why these mutations lead to different diseases, impacting clinical outcomes.

Area of Science:

  • Oncology
  • Genetics
  • Neurodevelopmental Biology

Background:

  • Investigating the dual role of specific gene mutations in driving both oncogenesis and neurodevelopmental disorders.
  • Understanding the increased cancer risk observed in individuals with neurodevelopmental conditions.

Purpose of the Study:

  • To elucidate the mechanisms by which mutations in key proteins (e.g., Ras, MEK, PI3K, PTEN, SHP2) lead to distinct pathological phenotypes.
  • To explore why identical mutations can result in cancer, neurodevelopmental disorders, or both.

Main Methods:

  • Literature review of studies examining mutations in oncogenic pathways.
  • Analysis of factors influencing disease phenotype determination.

Main Results:

  • Mutations in proteins like Ras, MEK, PI3K, PTEN, and SHP2 can manifest as cancer or neurodevelopmental disorders.
  • The same mutation can sometimes lead to both cancer and neurodevelopmental conditions.

Conclusions:

  • Cell type-specific expression of mutant proteins and pathway components is crucial.
  • The timing of mutation activation (embryonic vs. sporadic) influences disease outcome.
  • The absolute molecular dosage activated by mutations is a key determinant of pathological phenotypes, including cancer and developmental disorders.

More Related Videos

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis09:45

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

Published on: March 31, 2015

11.4K
Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines07:49

Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines

Published on: March 17, 2023

2.7K

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...
13.2K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.2K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.3K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

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.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.2K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.2K
Cancer02:18

Cancer

Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
50.5K