Tuesday, May 3, 2016

Landmark study in breast cancer deciphers new genes and mutations: A step closer to personalized cancer treatment.

With more than one million cases diagnosed annually, breast cancer is the most common class of cancer diagnosed in young and old women worldwide. It is responsible for more than 400 000 deaths per year making it the leading cause of cancer mortality in women.

The largest-ever study to sequence the whole genomes of breast cancers was conducted at Wellcome Trust Sanger Institute, one of the world's leading genome centers.

Scientist are claiming to have unraveled five new genes associated with breast cancer and 13 new mutational signatures that influence tumor development. Two landmark studies published in Nature and Nature Communications  reveal the genetic variations that  exist in breast cancer and identifying their place in genome sequencing.

The study led by Dr Serena Nik-Zainal of the Wellcome Trust Sanger Institute and her team sequenced 560 breast cancer genomes; 556 from women and four from men, including patients from Europe, US and Asia because of international collaboration.

All cancers have their origin in somatically acquired mutations in cell genomes that alter the functions of key cancer genes. An understanding of these events is very important in advancing prevention, early detection, monitoring and treatment of cancer. 

Mutational processes occurring from birth generating somatic mutations imprint particular patterns of mutations on cancer genomes, termed "mutation signatures". The researchers looked for mutational signatures in each patient's tumor.

Of the 560 breast cancers, 90 had germline (60) or somatic (14) inactivating mutations in BRCA1 (35) or BRCA2 (39) or showed methylation of the BRCA1 promoter (16).

Atleast 93 mutated cancer genes (31 dominant, 60 recessive, 2 uncertain) are implicated in genesis of the disease. Additional some infrequently mutated genes do exist, but majority of genes that harbor the majority of driver mutations are now known.

Dr Nik-Zainal said: "In the future, we'd like to be able to profile individual cancer genomes so that we can identify the treatment most likely to be successful for a woman or man diagnosed with breast cancer. It is a step closer to personalised healthcare for cancer."

Prof Sir Mike Stratton, the director of the Sanger Institute in Cambridge, said it was a "milestone" in cancer research.
He told the BBC: "There are about 20,000 genes in the human genome. It turns out, now we have this complete view of breast cancer - there are 93 of those [genes] that if mutated will convert a normal breast cell into a breast cancer cell. That is an important piece of information.

The list of mutant genes and their protein will be shared with universities, the pharmaceuticals, the biotech companies to start developing targeted therapy against them. One such drug Herceptin is already in use against specific mutation.

Identifying the exact place of mutation is important too. Collaborator Dr Ewan Birney, from the European Bioinformatics Institute, used computational techniques to analyse the sequence of genetic information held in each of the sample genomes. He said: "We know genetic changes and their position in the cancer genome influence how a person responds to a cancer therapy. For years we have been trying to figure out if parts of DNA that don't code for anything specific have a role in driving cancer development. This study both gave us the first large scale view of the rest of the genome, uncovering some new reasons why breast cancer arises, and gave us an unexpected way to characterize the types of mutations that happen in certain breast cancers."

But, the role of viruses and other microbes have not been explored. Additional infrequent mutation also plays a part in causation and they need to be identified. So, additional research and exploration analysis of whole-genome sequences from breast cancer patients will be required to complete the picture.


References:
Nik-Zainal S et al. Landscape of somatic mutations in 560 breast cancer whole genome sequencesis published in Nature 2016 published on 2 May doi: 10.1038/nature17676
Morganella S et al. The topography of mutational processes in breast cancer genomes is published in Nature Communications 2016 on 2 May doi: 10.1038/10.1038/NCOMMS11383

http://www.sanger.ac.uk/news/view/five-new-breast-cancer-genes-found

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