Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Rigged to Explode?

Published: Wednesday, April 11, 2012
Last Updated: Tuesday, April 10, 2012
Bookmark and Share
Inherited mutation links exploding chromosomes to cancer.

An inherited mutation in a gene known as the guardian of the genome is likely the link between exploding chromosomes and some particularly aggressive types of cancer, scientists at the European Molecular Biology Laboratory (EMBL), the German Cancer Research Centre (DKFZ) and the University Hospital, all in Heidelberg, Germany, have discovered.

Their study, published online in Cell, also presents the first whole genome sequence of a paediatric tumour: medulloblastoma, a brain cancer which is the second most common cause of childhood mortality in developed countries, where only car accidents cause more deaths in children.

Looking at the complete genome sequence of these tumours, the scientists found one or two chromosomes in each cell had countless parts in the wrong order, were missing some genes, and had extra copies of others.

Such extensive rearrangements suggested that those chromosomes had been shattered, like a bead necklace that is pulled too hard, and then wrongly reassembled.

But the scientists only found these telltale signs of chromosome explosion, or chromothripsis, in samples from a specific group of patients.

“All patients who had inherited a mutation in the TP53 gene showed signs of chromothripsis in their tumour cells, but none of the patients with normal TP53 did” says Jan Korbel, who led the genomics research at EMBL, “so this mutation must be involved either in shattering chromosomes, or in preventing the cell from reacting when a chromosome shatters.”

This strong link between the hereditary TP53 mutation and chromothripsis has implications for diagnosis and treatment.

“As clinicians, if we find evidence of chromothripsis in a medulloblastoma sample, we can now look for an inherited mutation in the TP53 gene” says Stefan Pfister, who led the work at the DKFZ, “and we know that any family members who also have the mutation should be screened regularly, as they’ll have a very high risk of developing particular types of cancer, including brain tumours.”

Cancer treatments often involve killing the tumour cells by damaging their DNA with chemo- or radiotherapy, but these treatments also affect healthy cells in the surrounding tissue.

If those cells have healthy copies of p53 - the protein encoded by TP53 - this gene will monitor the genome, and if it finds too much damage it will instruct the cells to stop dividing, sending them into the cellular equivalent of old age (senescence) or suicide (apoptosis).

But if a patient has inherited the TP53 mutation from their parents, all their cells will have faulty copies of this gene, including the cells surrounding the tumour.

Thus, those healthy cells will have trouble dealing with the DNA damage caused by such treatments, and could become cancerous themselves.

So the findings have immediate clinical implications in that such patients should not be given DNA-damaging chemotherapy or high-dose radiotherapy, since both would greatly increase the likelihood of secondary cancers.

The scientists believe that the TP53 mutation may also play a role in causing chromosomes to shatter in the first place, by shortening telomeres, the caps that keep chromosome ends from fraying.

This could make arms from different chromosomes more likely to get stuck to each other and shatter if they’re pulled in different directions.

Since telomeres naturally shorten with age, this could explain why, when the German scientists expanded their study to another cancer - an aggressive form of leukaemia in adults - they found that patients who had both a non-inherited TP53 mutation and evidence of chromothripsis were typically of an advanced age.

“Chromothripsis is thought to cause two to three percent of all human cancers,” says Korbel, “so if we can really prove how the TP53 mutation affects this process, it could have a big impact on our understanding of how healthy cells in the body turn into tumours.”

The study was undertaken as part of the International Cancer Genome Consortium (ICGC), an effort to study 50 different types of cancer worldwide.

“This study shows the power of combining genome sequencing and clinical expertise,” says Peter Lichter from DKFZ, and member of the ICGC scientific steering committee: “cancer genome sequencing can help to understand why patients can react so differently to cancer treatments, and may also lead to the development of new anti-cancer drugs.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More Than 4,600+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Scientists Discover Neural Mechanisms in Mouse Brains
Researchers at EMBL have discovered the neural mechanisms in mouse brains that indicate that we actively forget as we learn.
Saturday, March 19, 2016
Drugging Bacteria
Commonly used diabetes drug impacts gut bacteria more than disease itself.
Saturday, December 05, 2015
Finding Links and Missing Genes
A catalogue of large-scale genetic changes around the world.
Tuesday, October 06, 2015
Ages Apart
Multifaceted approach measured how brain and liver age differently.
Saturday, September 19, 2015
Iron Regulators Join War on Pathogens
Iron regulatory proteins (IRPs) play an important role in the body’s immune system.
Friday, July 17, 2015
EMBL Scientists Solve Decades-Old Cell Biology Puzzle
Behaviour of clathrin proteins, crucial for endocytosis, is clarified using new imaging techniques.
Saturday, June 20, 2015
It Runs in the Family
Distantly related viruses share a common machinery for replication.
Saturday, May 23, 2015
The Battle for Iron
Understanding anaemias of the chronically ill.
Saturday, February 07, 2015
Protecting us from Our Cells
Growth factor boosts natural defence against auto-immune disorders.
Tuesday, November 04, 2014
Double Act: How a Single Molecule Can Attract and Repel Growing Brain Connections
The 3D structure of Netrin-1 bound to DCC shows Netrin-1 binds to two DCC molecules in different ways.
Saturday, August 09, 2014
Cancer by Remote-Control
Overlooked DNA shuffling drives deadly paediatric brain tumour.
Tuesday, June 24, 2014
Wired for Change
First steps of gene regulation evolution revealed.
Monday, August 05, 2013
More than Meets the Eye
‘Transformer’ protein makes different sized transport pods.
Tuesday, May 29, 2012
Multi-tasking Protein Provides New Approaches for Anti-tuberculosis Drugs
Scientists from EMBL reveal new insights into the workings of enzymes from a group of bacteria including Mycobacterium tuberculosis.
Thursday, February 17, 2011
The Human Genome’s Breaking Points
Comprehensive catalogue uncovers genetic sequence of large-scale differences between human genomes.
Wednesday, February 16, 2011
Scientific News
Platelets are the Pathfinders for Leukocyte Extravasation During Inflammation
Findings from the study could help in the prevention and treatment of inflammatory pathologies.
ASMS 2016: Targeting Mass Spectrometry Tools for the Masses
The expanding application range of MS in life sciences, food, energy, and health sciences research was highlighted at this year's ASMS meeting in San Antonio, Texas.
Benchtop Automation Trends
Gain a better understanding of current interest in and future deployment of benchtop automated systems.
Manufactured Stem Cells to Advance Clinical Research
Clinical-grade cell line will enable development of new therapies and accelerate early-stage clinical research.
Dengue Virus Exposure May Amplify Zika Infection
Researchers at Imperial College London have found that the previous exposure to the dengue virus may increase the potency of Zika infection.
Gender Determination in Forensic Investigations
This study investigated the effectiveness of lip print analysis as a tool in gender determination.
Identifying Novel Types of Forensic Markers in Degraded DNA
Scientists have tried to verify the nucleosome protection hypothesis by discovering STRs within nucleosome core regions, using whole genome sequencing.
Proteins in Blood of Heart Disease Patients May Predict Adverse Events
Nine-protein test shown superior to conventional assessments of risk.
Higher Frequency of Huntington's Disease Mutations Discovered
University of Aberdeen study shows that the gene change that causes Huntington's disease is much more common than previously thought.
Starving Stem Cells May Enable Scientists To Build Better Blood Vessels
Researchers from the University of Illinois at Chicago College of Medicine have uncovered how changes in metabolism of human embryonic stem cells help coax them to mature into specific cell types — and may improve their function in engineered organs or tissues.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,600+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!