Related Experiment Video
Updated: Feb 17, 2026
Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH
Published on: August 19, 2014
Whole chromosome loss and associated breakage-fusion-bridge cycles transform mouse tetraploid cells
Rozario Thomas1,2, Daniel Henry Marks2, Yvette Chin2
1BCMB Program, Weill Cornell Graduate School of Medical Sciences (WCGSMS), New York, NY, USA.
Abstract:
Whole chromosome gains or losses (aneuploidy) are a hallmark of ~70% of human tumors. Modeling the consequences of aneuploidy has relied on perturbing spindle assembly checkpoint (SAC) components, but interpretations of these experiments are clouded by the multiple functions of these proteins. Here, we used a Cre recombinase-mediated chromosome loss strategy to individually delete mouse chromosomes 9, 10, 12, or 14 in tetraploid immortalized murine embryonic fibroblasts. This methodology also involves the generation of a dicentric chromosome intermediate, which subsequently undergoes a series of breakage-fusion-bridge (BFB) cycles. While the aneuploid cells generally display a growth disadvantage in vitro, they grow significantly better in low adherence sphere-forming conditions and three of the four lines are transformed in vivo, forming large and invasive tumors in immunocompromised mice. The aneuploid cells display increased chromosomal instability and DNA damage, a mutator phenotype associated with tumorigenesis in vivo Thus, these studies demonstrate a causative role for whole chromosome loss and the associated BFB-mediated instability in tumorigenesis and may shed light on the early consequences of aneuploidy in mammalian cells.
Insights
Whole chromosome loss, a common feature in human tumors, can drive cancer development. This study demonstrates that aneuploidy and subsequent chromosomal instability promote tumorigenesis in mice.
Area of Science:
- Genetics
- Cancer Biology
- Cell Biology
Background:
- Aneuploidy (whole chromosome gains or losses) is prevalent in human cancers.
- Previous models of aneuploidy used spindle assembly checkpoint (SAC) perturbations, complicating interpretation due to SAC protein multifunctionality.
Purpose of the Study:
- To investigate the direct consequences of whole chromosome loss on tumorigenesis.
- To model aneuploidy using a novel chromosome deletion strategy.
Main Methods:
- Utilized Cre recombinase-mediated deletion to remove specific mouse chromosomes (9, 10, 12, 14) in tetraploid murine embryonic fibroblasts.
- Induced breakage-fusion-bridge (BFB) cycles via dicentric chromosome intermediates.
- Assessed cell growth in vitro and in vivo tumor formation in immunocompromised mice.
Main Results:
- Aneuploid cells exhibited a general in vitro growth disadvantage but enhanced growth in sphere-forming conditions.
- Three of four aneuploid cell lines transformed in vivo, forming invasive tumors.
- Aneuploid cells showed increased chromosomal instability, DNA damage, and a mutator phenotype.
Conclusions:
- Whole chromosome loss, coupled with BFB-mediated instability, causally contributes to tumorigenesis.
- This model provides insights into the early stages of aneuploidy-driven cancer development in mammalian cells.
More Related Videos
10:14Detection of Inter-chromosomal Stable Aberrations by Multiple Fluorescence In Situ Hybridization mFISH and Spectral Karyotyping SKY in Irradiated Mice
Published on: January 11, 2017
09:24Preparation of Meiotic Chromosome Spreads from Mouse Oocytes for Assessment of Synapsis and Recombination
Published on: July 18, 2025
Related Concept Videos
02:08Gene Conversion
01:49Meiosis I
02:04Fixing Double-strand Breaks
02:57Meiosis vs. Mitosis
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
01:29Nondisjunction
01:21Nondisjunction