Genetics of breast cancer progression mapped

The genetic landscape of breast cancer is much more complicated than previously hoped, according to the authors of two analyses of multiple tumour genomes.

The first study, published in Nature, mapped all the protein-coding genes in the genomes of 100 tumours to inform what the team describe as a 'sobering perspective' on the diversity of the disease.

Researchers found 73 different mutation combinations in the samples, including alterations in nine genes not previously known to drive breast cancer development.

'In 28 cases we found only a single driver, but the maximum number of driver mutations in an individual cancer was six', said study leader Professor Mike Stratton, director of the Wellcome Trust Sanger Institute in Cambridgeshire.

'If we consider three breast cancers, each with four driver mutations: they might share none of those driver mutations - so each is a different genetic 'animal'', Professor Stratton continues. 'They are different cancers driven by different genes. We need to classify them as carefully as we can. This study is a step towards that goal'.

This is the first study to analyse 'driver' mutations - as opposed to the 'passenger' mutations that are found in breast cancers, but don't contribute to the disease's development - in this level of detail. With the nine newly identified genes, the total number of known driver genes for breast cancer is 40. Seven of these were mutated in over 10 percent of these 100 cases.

Dr Christina Curtis, an assistant professor of preventive medicine at the Keck School of Medicine at USC told the LA Times that finding new combinations of driver genes is an important part of understanding the way these mutations cause breast cancer. 'It seems we're getting closer', she said. 'With each study we're getting a new vantage point'.

The second study, published in the journal Cell, analysed the progression of 21 breast cancer tumours in more detail.

It found that a rapid 'storm' of mutations may be a major cause of breast cancer. They reported that mutations built up slowly at first, but then increased as time went on, with massively mutated localised areas of DNA appearing suddenly.

'What emerges is a really complex landscape of mutation, where each cancer seems to have been generated by a different combination of mutation processes', said Professor Stratton.