Israeli researchers developing BRCA 'radiation' test
Tuesday 22 January 2013
Rather than directly analysing an individual’s DNA, the scientists propose the new test could identify at-risk people with mutations that current methods find hard to spot.
But others cautioned that the method, while promising, would need significant development and testing before it could replace existing methods, which rely on DNA sequencing.
Discovered in the 1980s, the BRCA1 and BRCA2 genes are found in all human cells, and normally make proteins that are involved in cell division and DNA repair - two processes that go wrong in cancer.
As a result, people who inherit faulty copies of either gene have a significantly increased risk of breast, ovarian and prostate cancers, and these cancers often run in their families. About five in every hundred breast cancers are thought to be caused by an inherited BRCA gene.
At the moment, DNA samples from members of affected families can be tested, and carriers offered extra monitoring or treatment.
But the test relies on being able to predict whether a fault is likely to be harmful, by comparing the DNA analysis against previously known mutations.
This has disadvantages, says study author Dr Asher Salmon, from the the Hadassah Hebrew University Medical Center in Jerusalem.
"The current tool for mutation detection is gene sequencing, which is expensive, time-consuming and, in many cases, lacking clear and decisive clinical decision making information," he said.
"In many cases, [it] identifies a mutation, but we do not know if the mutation is neutral or harmful."
Since they are unable to repair damaged DNA, cells that contain faulty BRCA genes are more sensitive to radiation. So Salmon's team tested whether this response could be used as a marker for faulty BRCA genes.
Initially analysing blood samples from nine healthy women with a mutated BRCA1 gene and eight healthy women with a mutated BRCA2 gene, they developed a 'signature' of the cells' response to radiation, made up of a number of genes that were switched on or off in response to radiation.
They then confirmed this signature's presence in radiation-treated blood samples from an independent group of 40 women who were carriers of mutated BRCA1 and/or BRCA2, but absent from 17 non-carrier women.
The test correctly identified 95 percent of BRCA carriers, and 88 percent of non-carriers.
According to Salmon, the test can show whether an individual carries a cancer-linked fault, regardless of the specific mutation they carry. In addition, it could be extremely useful across the developing world, where expensive gene-sequencing equipment may not be accessible.
However, Cancer Research UK’s Dr Julie Sharp urged caution.
"This is a very preliminary finding. The current test - DNA sequencing - is easy to standardise across different labs, whereas this new method would require substantial expertise and training to make sure its results were as consistent between labs.
"And we don't currently know whether there are indeed significant numbers of families out there who are unidentified carriers of BRCA mutations, who would not be picked up by existing methods."
"That said, if further development goes as planned, this could be a useful technique to spot BRCA mutation carriers under certain circumstances."
The research is published in the journal Cancer Prevention Research
- Salmon A.Y. et al. Determination of Molecular Markers for BRCA1 and BRCA2 Heterozygosity Using Gene Expression Profiling. Cancer Prev Res (2012) DOI: 10.1158/1940-6207.CAPR-12-0105
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