<XML><RECORDS><RECORD><REFERENCE_TYPE>0</REFERENCE_TYPE><REFNUM>8134</REFNUM><AUTHORS><AUTHOR>Kote-Jarai,Z.</AUTHOR><AUTHOR>Matthews,L.</AUTHOR><AUTHOR>Osorio,A.</AUTHOR><AUTHOR>Shanley,S.</AUTHOR><AUTHOR>Giddings,I.</AUTHOR><AUTHOR>Moseews,F.</AUTHOR><AUTHOR>Locke,I.</AUTHOR><AUTHOR>Evans,G.</AUTHOR><AUTHOR>Girolami,M.</AUTHOR><AUTHOR>Williams,R.</AUTHOR><AUTHOR>Campbell,C.</AUTHOR></AUTHORS><YEAR>2006</YEAR><TITLE>Accurate Prediction of BRCA1 and BRCA2 heterozygous genotype using expression profiling after induced DNA damage</TITLE><PLACE_PUBLISHED>Clinical Cancer Research, Vol. 12, No. 13, pp. 3896 - 3901</PLACE_PUBLISHED><PUBLISHER>N/A</PUBLISHER><LABEL>Kote-Jarai:2006:8134</LABEL><KEYWORDS><KEYWORD>breast cancer</KEYWORD></KEYWORDS<ABSTRACT>Germline mutations in the BRCA1 and BRCA2 genes predispose women to an increased risk of breast and ovarian cancer. Both genes have important roles in DNA damage repair and have been implicated in gene expression regulation. In this study we have investigated the differential gene expression changes following radiation-induced DNA damage in healthy cells from BRCA1/2 mutation carriers compared with non-carrier controls using high-density microarray technology. Short-term primary fibroblast cultures were established from skin biopsies from 10 BRCA1 and 10 BRCA2 mutation carriers and 10 controls, all of whom had previously had breast cancer. The cells were subjected to 15 Gy high dose rate ionizing irradiation to induce DNA damage. RNA was extracted from all cell cultures pre-irradiation and at 1 hour post-irradiation. For expression profiling, we used 15 K spotted cDNA microarrays manufactured by the Cancer Research UK DNA Microarray Facilitiy at The Institute of Cancer Research. A support vector machine classifier (SVM) was used to identify the best prediction features for the BRCA1 and the BRCA2 heterozygous genotype. To investigate prediction accuracy we used a non-probabilistic classifier (SVM) and a probabilistic classifier (a Gaussian Process classifier). These both achieved high test accuracy, at 90-100%, in the task of distinguishing BRCA1 and BRCA2 mutation carriers from non-carriers following radiation induced DNA damage, an effect which could not be achieved without irradiation. We conclude that after irradiation induced DNA damage, BRCA1 and BRCA2 heterozygous cells have a distinctive expression phenotype reflecting the function of these genes in DNA damage repair. This may have a future role in predicting genotypes with applications to clinical detection and classification of mutations.</ABSTRACT></RECORD></RECORDS></XML>