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Breakthrough Breast Cancer scientists have unravelled the complete genetic code of the most common type of hereditary breast cancer for the first time. Scientists from the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR) have fully sequenced the DNA of two breast cancers caused by a faulty BRCA1 gene. Surprisingly, changes in the genetic code of the two tumours looked almost entirely different from one another. This information can now help scientists identify better treatment strategies for patients with a faulty BRCA1 gene.
The study today also produced preliminary results identifying three new breast cancer genes – DAPK3, TMEM135 and GATA4. These are tumour suppressor genes which, when mutated, could be involved in causing breast cancer or driving its growth. The results are published today online in The Journal of Pathology.
Hereditary breast cancer accounts for up to 10% of all breast cancers, or around 4,500 cases in the UK each year. The most common cause is a faulty BRCA1 gene. Women with a BRCA1 mutation have around up to 85 per cent risk of developing breast cancer during their lifetime. BRCA1 breast cancers are usually aggressive and typically do not benefit from targeted drugs such as tamoxifen and Herceptin (trastuzumab).
Study co-author, Professor Jorge Reis-Filho, from the Breakthrough Breast Cancer Research Centre at the ICR, said:
“This research has big implications for how we treat hereditary breast cancer in the future. We often consider patients with a faulty BRCA gene as one group but our work shows that each tumour can look very different from each other genetically. Now we understand this, we can start to identify the best treatment strategies to save more lives of hereditary breast cancer patients.”
The scientists looked at two tumours, both caused by a faulty BRCA1 gene, with one classified as hormone receptor negative and one hormone receptor positive. They then tracked all of the genetic mutations in both of the tumours and found only one similarity in addition to the initial BRCA1 fault. All of the additional genetic alterations were different. The hormone receptor negative tumour had around twice as many mutations as the other, underlining the differences that have occurred in their DNA.
Based on the alterations found in these two cases, the scientists scanned the genome of another group of breast cancers and identified three genes that were found to be altered in several other tumours. Although these genes have not previously been linked to breast cancer, the results suggest they may drive the identification of additional subtypes of breast cancer.
Study co-author Dr Rachael Natrajan, from the Breakthrough Breast Cancer Research Centre at the ICR, said:
“It is exciting to find new genes which could be involved in causing and driving breast cancer. Now these have been identified we have to do more work to find out the role that they play. Ultimately, this knowledge could help us develop new treatments that target the specific defects of each patient’s disease.”
The study also included teams from the Institut Curie in France, the University Medical Center Utrecht in the Netherlands, The Cancer Research UK London Research Institute in London and the University of Nottingham.
We would like to thank Walk the Walk for being Principal funders of the work of Professor Reis-Filho’s laboratory. Walk the Walk has given over £16 million to Breakthrough Breast Cancer since 1996.