Navigation Links
Rigged to explode?
Date:1/19/2012

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 today 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."


'/>"/>

Contact: Sonia Furtado Neves
sonia.furtado@embl.de
European Molecular Biology Laboratory
Source:Eurekalert  

Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Rigged to explode?
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... Apple ... care services, staged a mock evacuation of the facility as part of a disaster ... Fire Department, Echo Hose EMS and Shelton City Emergency Manager, as well as the ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Global Healthcare Management’s ... Alexandria Park in Milford, NJ. This free event, sponsored by Global Healthcare Management’s ... The fun run is geared towards children of all ages; it is a ...
(Date:10/13/2017)... ... October 13, 2017 , ... “The Journey: From the ... danger possible to save lost souls in the Philippines. “The Journey: From the Mountains ... a dedicated teacher of the Bible. She has taught all ages and currently teaches ...
(Date:10/12/2017)... ... October 12, 2017 , ... Planet Fitness, one of the largest and ... plans to open a flagship location in Covington, LA at 401 N. U.S. Highway ... store next to Office Depot in the Holiday Square shopping center. Its location allows ...
(Date:10/12/2017)... ... 2017 , ... Asante, a nationally recognized health system in ... existing home health joint venture through an agreement, effective October 1, 2017, to ... home health company with Asante, delivering clinically integrated care, for the past eight ...
Breaking Medicine News(10 mins):
(Date:10/10/2017)... -- NDS received FDA 510(k) clearance in May 2017 for its highly ... designed for endoscopy environments. An innovative secondary monitor solution, ZeroWire ... support the improvement of patient outcomes, procedural efficiency, and the lowering ... ... ...
(Date:10/4/2017)... 4, 2017  South Korean-based healthcare product Development Company ... "cprCUBE" on Kickstarter. The device will educate the user ... with better efficiency compared to the dated and pricey ... on efficacy of the compression for a more informed ... goal to raise $5,000. ...
(Date:10/2/2017)... 2017  Eli Lilly and Company (NYSE: ... third quarter of 2017 on Tuesday, October 24, 2017. ... day with the investment community and media to further ... call will begin at 9 a.m. Eastern time. Investors, ... webcast of the conference call through a link that ...
Breaking Medicine Technology: