Navigation Links
Broken genomes behind breast cancers
Date:12/23/2009

The first detailed search of breast cancer genomes to uncover genomic rearrangements is published today. The team characterised the ways in which the human genome is broken and put back together in 24 cases of breast cancer.

Rearrangements involve reshuffling and reorganisation of the genome and include deletions, duplications and novel juxtaposition of DNA sequences. The study shows that breast cancer samples can differ greatly in the extent to which they are subject to genomic rearrangements: some are relatively undisturbed whereas others are fractured extensively and then reassembled with more than 200 rearrangements present.

While it is known that the majority of cancer genes important in blood cancers are activated by rearrangement, the role of this process in the common adult cancers is much less clear. This new study builds on pioneering work from the team using next generation sequencing to characterise comprehensively rearrangements in adult solid tumours.

"We have looked at the level of the DNA sequence at just how splintered and reorganised the genome is in many breast cancers. We were, frankly, astounded at the number and complexity of rearrangements in some cancers." says Professor Mike Stratton of the Wellcome Trust Sanger Institute. "Just as important, the genomes were different from each other, with multiple distinctive patterns of rearrangement observed, supporting the view that breast cancer is not one, but several diseases."

The information obtained from this study will add a new dimension to tumour classification and thus refine diagnosis and treatment.

In the study, the team used next-generation DNA sequencing to produce maps of genome rearrangements in 24 breast cancer samples, which were chosen to include the major subtypes of breast cancer and also included examples of breast cancers arising in BRCA1 and BRCA2 breast cancer families.

One breast cancer showed just a single genomic rearrangement while others showed more than 200. The study provides detailed insights into the ways that the genome in some cancers have broken and also the processes that were used by the cancer cell in gluing the broken bits of genome back together again.

"It looks as though some breast cancers have a defect in the machinery that maintains and repairs DNA and this defect is resulting in large numbers of these abnormalities," says Dr Andy Futreal of the Wellcome Trust Sanger Institute. "At the moment we do not know what the defect is or the abnormal gene underlying it, but we are seeing the result of its malfunction in the hideously untidy state of these genomes. Identifying the underlying mutated cause will be central to working out how some breast cancers develop."

The broad groups of rearrangement were associated with different subtypes of breast cancer: HER2 positive breast cancers those that are responsive to herceptin have similar patterns of disruption. By the same measure, triple-negative breast cancers, which don't respond to treatment with herceptin or hormones, looked similar.

The size of the DNA regions that are deleted, duplicated or removed ranges from a few hundred letters of DNA code to several millions. Most changes were rearrangements within the same chromosome, but there were also a substantial number involving the joining of two different chromosomes.

Dissecting out the complexity and the diversity of the breast cancer genomes is important for understanding how the cancers arise. Importantly, however, the apparent loss of DNA repair systems raises the possibility of new therapeutic opportunities in some breast cancers.

"It appears that in different subtypes of breast cancers, distinct mechanisms of DNA repair are impaired, leading to different types of genomic disorganisation," suggests Dr Jorge Reis-Filho, team leader from the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research.

"If we damage further an already-faulty DNA repair system using tailored therapies, one can kill tumour cells selectively, without harming normal cells. There are already some highly interesting results suggesting that breast cancers with defects in DNA repair are more sensitive to drugs that cause additional DNA damage."


'/>"/>

Contact: Don Powell
press.officer@sanger.ac.uk
44-122-349-6928
Wellcome Trust Sanger Institute
Source:Eurekalert

Related medicine news :

1. Insurance Commissioner Says Federal Health Care Reform Necessary to Fix a Broken System
2. Ibuprofen Rated Best for Pain of Broken Arms
3. With a Broken Hip Comes Higher Risk for Dying
4. New AMA Ad Emphasizes Common Ground on Health Reform, Shares Vision to Fix Broken System
5. Nation Takes a Big Step Toward Learning Which Medical Treatments Work Best, a Major Advance in Fixing Our Broken Health-Care System
6. National Survey Reveals a Broken System for Chronic Disease Sufferers; National Council on Aging and Health Experts Explore Self-Care as a Viable, Consumer Focused Option for Health Reform
7. Physicians mending broken hearts
8. Registry Created for Broken Heart Syndrome
9. Using a Balloon to Repair a Broken Back
10. The Bold Leadership America Needs to Confront a Broken Healthcare System
11. Nurses to Congress: Expanding Medicare Could Reverse Job Losses, and Repair Our Broken Healthcare System and Safety Net
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/12/2016)... ... February 12, 2016 , ... ... initiative—the Siemens Foundation-PATH Ingenuity Fellowships—to develop the advanced skills needed to introduce ... from U.S. universities who will draw from Siemens’ deep knowledge of product ...
(Date:2/12/2016)... (PRWEB) , ... February 12, 2016 , ... ... 29, 2016 — 1:30 p.m. – 3:00 p.m. EST, http://www.fdanews.com/fixeddosecombination ... the life cycle of pharmaceutical products, garnering increased attention from all stakeholders in ...
(Date:2/12/2016)... (PRWEB) , ... February 12, 2016 , ... Coco Libre, ... participation in Red Carpet Events LA GRAMMY’s Style Lounge Event. Coco Libre will offer ... to stay hydrated before the big event. The invitation-only gifting suite, held this year ...
(Date:2/12/2016)... ... February 12, 2016 , ... ... (WaaS), today announced the integration of Clarity Intelligence Platform (CIP) into Cielo®, a ... offer real-time business intelligence (BI) to their small and medium business (SMB) clients. ...
(Date:2/12/2016)... ... ... AssureVest Insurance Group, a locally owned insurance firm with offices serving Washington ... earmarked to purchase computers and software for Mrs. Harrison’s 2nd and 3rd grade special ... low-income area and has more than 60 2nd and 3rd graders with learning disabilities. ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... 12 februari 2016 AAIPharma Services ... leverancier van productie en ontwikkeling op maat ... vandaag een uitbreiding aan van steriele vul- ... in Charleston, SC . ... meerdere recente investeringen. http://photos.prnewswire.com/prnh/20150806/256637LOGO ...
(Date:2/12/2016)... BUDAPEST , Ungarn, February 12, 2016 ... ein Medizintechnikunternehmen, das sich auf den ungedeckten ... gab heute positive Ergebnisse seines klinischen Forschungsprogramms ... und Asthma-Patienten beschäftigt, ergab Verbesserungen ihrer respiratorischen ... Indiso ltd , ein Medizintechnikunternehmen, das ...
(Date:2/11/2016)... - Cardiac Marker Diagnostic ... and Cancer Therapy. - European Point of Care ... - Key Diagnostic Testing Markets. - Molecular ... Genetic Testing. - Molecular Diagnostics in Infectious Disease ... Diagnostic Products World Markets. - Point of Care ...
Breaking Medicine Technology: