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:12/7/2016)... ... December 07, 2016 , ... Baciocco Brothers Insurance Agency, a ... the Sacramento/Folsom region, is initiating a charity event to raise support and awareness ... Chance treatment center in Sacramento works to provide area teens and families with ...
(Date:12/7/2016)... ... ... A. Kevin Spann Insurance, a New York-based firm offering insurance and financial consultation ... drive to raise funds that will benefit the Marine Corps League. , The Marine ... Corpsmen. Working closely with the MCL, the A. Kevin Spann team plans to generate ...
(Date:12/7/2016)... ... 2016 , ... Facial plastic surgeon, Dr. John D. Rachel of Timeless ... proceeds to two local organizations: North Chicago Animal Control and Friends and Our House ... team of authorized and trained volunteers who support rescued animals held in the City ...
(Date:12/7/2016)... ... December 07, 2016 , ... The medical profession is well aware that heart ... major study analyzing heart attacks among 138,602 people recorded a 35% higher number of ... would all agree of course–no time of year is a good time for a ...
(Date:12/7/2016)... ... December 07, 2016 , ... Maureen McLaughlin, LA.c., a certified ... Associates of Connecticut (RMACT). McLaughlin brings nearly 20 years of experience with fertility ... patients realize their family building goals. Acupuncture helps fertility patients by ...
Breaking Medicine News(10 mins):
(Date:12/6/2016)... -- Alopexx Oncology, LLC announced data from a Phase I ... composed of interleukin-2 and a CD20-targeting monoclonal antibody. The ... as Rituxan and maintains the activities of both the ... tumor targeting, engagement of the immune system, and induction ... study (abstract #95954) were presented at the 58 th ...
(Date:12/6/2016)... Dec. 6, 2016 Diabetes & Obesity Drug ... and obesity disease cluster is currently dominated by therapeutics ... 2 diabetes mellitus (T2DM), and the majority of the ... products, is attributable to these indications. While products indicated ... presence, there are a large number of these products ...
(Date:12/6/2016)... The pen needles market is projected to reach USD ... 2016, growing at a CAGR of 11.2% during the ... years, the pen needles market has witnessed various technological ... for safety injections in the healthcare industry. These advancements ... with an aim to reduce pain, increase comfort, and ...
Breaking Medicine Technology: