Related Experiment Video

Updated: Aug 12, 2025

Generation and Isolation of Cell Cycle-arrested Cells with Complex Karyotypes
05:22

Generation and Isolation of Cell Cycle-arrested Cells with Complex Karyotypes

Published on: April 13, 2018

10.5K

Oncogene-like addiction to aneuploidy in human cancers

Vishruth Girish1,2, Asad A Lakhani3, Christine M Scaduto3

  • 1Yale University School of Medicine, New Haven, CT 06511.

Biorxiv : the Preprint Server for Biology
|January 30, 2023
PubMed

Insights

Aneuploidy, an abnormal chromosome number in cancer, is crucial for tumor growth. Researchers developed tools to remove specific aneuploidies, revealing chromosome 1q gain drives cancer by affecting MDM4 and TP53 signaling.

Area of Science:

  • Cancer biology
  • Genomics
  • Chromosomal instability

Background:

  • Aneuploidy is common in cancers, but its role in tumor development remains debated.
  • Understanding the functional impact of specific aneuploidies is critical for cancer research.

Approach:

  • Developed ReDACT (Restoring Disomy in Aneuploid cells using CRISPR Targeting), a CRISPR-based toolset for precise chromosome engineering in cancer cells.
  • Created isogenic cancer cell lines with and without specific aneuploidies, including chromosome 1q trisomy.
  • Investigated the mechanistic link between 1q gain, MDM4 expression, and TP53 pathway suppression.

Key Points:

  • Trisomy of chromosome 1q is essential for the malignant growth of cancers with this alteration.
  • Chromosome 1q gain leads to increased MDM4 expression and suppressed TP53 signaling.
  • TP53 mutations and 1q aneuploidy are mutually exclusive in human cancers, suggesting distinct oncogenic pathways.

Conclusions:

  • Specific aneuploidies, termed "aneuploidy addictions," play essential roles in tumorigenesis.
  • Targeting these aneuploidy addictions presents a potential novel therapeutic strategy for cancer treatment.

More Related Videos

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel08:29

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel

Published on: May 14, 2018

10.0K
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.3K

Related Concept Videos

Nondisjunction01:21

Nondisjunction

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers.  Nondisjunction is common during anaphase I or anaphase II of meiosis.  Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold...
3.9K
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...
12.4K
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...
9.1K
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...
4.3K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
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,...
4.2K