with tumours in two relatives, and a few with two tumours in one person) to see whether there was a loss of genetic material close to the BRCA genes and whether the same loss was seen in the same place in both tumour samples. All genes and DNA material come in pairs, and when genetic material from one half of a pair is lost in a cancer cell it is called loss of heterozygosity (LOH). Losses of portions of genetic material occur at random in all cancers (because genetic material is unstable in cancer), and so there is always a background level of LOH found in sporadic (i.e. non-hereditary) cancers. The Nottingham team knew that LOH can arise randomly in sporadic breast cancers, but they proposed that if the same LOH was detected in the same place in two different tumours in a family it might point to an underlying hereditary mutation in a breast cancer gene.
Mr. Cid chose five spots or markers close to the BRCA1 and BRCA2 genes to search for LOH; this enabled him to maximise the chances of gaining useful information with minimum effort.
He matched the results of the LOH tests with the results from standard genetic mutational analysis. In 50% (four out of eight) of cases where LOH predicted a mutation in BRCA1 or BRCA2, this was confirmed by mutation analysis, he said. In the remaining 50%, mutations may still be present, but the current technique of genetic mutational analysis is not perfect and can not detect all mutations it usually manages to detect between 50-70% of mutations.
We also carried out LOH testing in 52 control breast cancer cases that is, cases of breast cancer in post-menopausal women with no family history present who were therefore very unlikely to have a hereditary gene mutation. In this group we obtained blood from nine people, a lower background LOH level was present and no mutations were found, as one would expect.
This study has shown that where there is LOH in the same place at two or more markers iPage: 1 2 3 Related biology news :1
Contact: Emma Mason
Federation of European Cancer Societies
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