Related Experiment Video
Updated: Dec 7, 2025
06:06
High-Throughput Dissociation and Orthotopic Implantation of Breast Cancer Patient-Derived Xenografts
Published on: December 20, 2024
1.1K
Chromothripsis in Human Breast Cancer
Michiel Bolkestein1, John K L Wong2, Verena Thewes2,3
1Group Genome Instability in Tumors, DKFZ, Heidelberg, Germany.
Cancer Research
|September 25, 2020
Summary
Chromothripsis, a major genomic rearrangement event, is a significant driver in human breast cancer development. This study found it affects over 60% of metastatic breast cancers, impacting key genes and tumor evolution.
Area of Science:
- Genomics
- Cancer Biology
- Genomic Instability
Background:
- Chromothripsis is a catastrophic genomic event causing extensive rearrangements.
- It is widely considered an early event in tumor development and onset.
Purpose of the Study:
- To analyze the prevalence and impact of chromothripsis in human breast cancers.
- To investigate the role of chromothripsis in tumor evolution and identify associated genetic alterations and mutational signatures.
Main Methods:
- Whole-genome and whole-exome sequencing of 252 human breast cancer samples.
- Analysis of patient cohorts including metastatic, primary, and relapsed tumors, plus longitudinal pairs.
- Investigation of chromothripsis patterns, affected genes, and associated mutational signatures.
Main Results:
- Chromothripsis affects a substantial proportion of breast cancers, exceeding 60% in metastatic cases.
- Multiple chromosomes are frequently involved, with key genes like CCND1, ERBB2, CDK12, and BRCA1 altered.
- Recurrent fusions driven by chromothripsis were identified, linked to specific mutational signatures and signaling pathway activation.
Conclusions:
- Chromothripsis is a major driving event in human breast cancer.
- It significantly contributes to tumor evolution through recurrent gene fusions and altered mutational landscapes.
- Understanding chromothripsis provides critical insights into breast cancer pathogenesis.
More Related Videos
Related Concept Videos
02:21Cancers Originate from Somatic Mutations in a Single Cell
14.2K
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...
14.2K
01:20The Retinoblastoma Gene
4.5K
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,...
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,...
4.5K
02:37Restarting Stalled Replication Forks
6.1K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.1K
02:55The Nucleolus
10.0K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
10.0K