Related Experiment Video
Updated: Dec 10, 2025
07:42
Chromosome Preparation From Cultured Cells
Published on: January 28, 2014
83.3K
Pervasive chromosomal instability and karyotype order in tumour evolution
Thomas B K Watkins1, Emilia L Lim1,2, Marina Petkovic3
1Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Nature
|September 4, 2020
Summary
Chromosomal instability fuels cancer evolution by creating diverse genetic changes. This study reveals these changes, somatic copy number alterations, often occur in parallel and are enriched in metastatic tumors.
Area of Science:
- Genomics
- Cancer Biology
- Evolutionary Biology
Background:
- Chromosomal instability (CIN) drives cancer evolution through dynamic changes in chromosome number and structure.
- Somatic copy number alterations (SCNAs) generated by CIN provide the genetic diversity for tumor adaptation and progression.
Purpose of the Study:
- To investigate the patterns and consequences of CIN-driven SCNA heterogeneity across diverse cancer types.
- To identify recurrent SCNA events and their timing relative to key genomic events like whole-genome doubling.
- To assess the enrichment of specific SCNAs in metastatic tumors.
Main Methods:
- Multi-sample phasing and SCNA analysis of 1,421 samples from 394 tumors across 22 types.
- Analysis of an independent cohort of 1,024 metastatic samples.
- Comparative analysis of SCNA patterns in primary versus metastatic settings.
Main Results:
- Continuous CIN leads to pervasive SCNA heterogeneity, with parallel evolutionary events affecting key genes in 37% of tumors.
- Most SCNA losses preceded whole-genome doubling (clonal in 49% of tumors), but HLA and 8p losses occurred sub-clonally even post-doubling.
- Thirteen focal SCNAs, including MYC and CCND1 amplifications, were enriched in metastatic samples, indicating their role in metastasis.
Conclusions:
- CIN drives ordered, parallel SCNA events throughout tumor evolution, contributing to heterogeneity.
- Specific SCNAs are selected for during tumor progression and metastasis, highlighting their functional importance.
- Understanding SCNA patterns can inform targeted therapies and predict metastatic potential.
Related Concept Videos
02:21Cancers Originate from Somatic Mutations in a Single Cell
14.3K
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...
14.3K
02:07Tumor Progression
7.1K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
7.1K
01:17Karyotyping
67.2K
Overview
67.2K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
9.2K
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...
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
01:12Loss of Tumor Suppressor Gene Functions
5.6K
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...
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...
5.6K