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Association between loss of heterozygosity of BRCA1 and BRCA2 and morphological attributes of sporadic breast cancer

Hanby, AM; Kelsell, DP; Potts, HW; Gillett, CE; Bishop, DT; Spurr, NK; Barnes, DM; (2000) Association between loss of heterozygosity of BRCA1 and BRCA2 and morphological attributes of sporadic breast cancer. INT J CANCER , 88 (2) 204 - 208.

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Abstract

Germline mutations in the breast cancer-associated genes BRCA1 and BRCA2 confer a lifetime risk of malignancy. Distinctive morphological features have been attributed to these familiar tumours; however, in sporadic breast cancer, the inter-relationship between loss of heterozygosity (LOH) of these loci and tumour morphology remains to be fully elucidated. We studied a series of 120 sporadic breast carcinomas using microsatellite markers to identify LOH of BRCA1, BRCA2, p53 and PTEN, The associations between loss at each of the loci were examined and related to tumour morphology. LOH of the 4 loci did not occur independently; there were highly significant associations between LOH of BRCA1 and both BRCA2 (p < 0.001) and p53 (p < 0.001). LOH at all 4 loci was significantly associated with a high degree of nuclear pleomorphism, Tumours with LOH of BRCA1 also had high mitotic indices, few tubules and a paucity of DCIS, all of which are morphological features similar to those described for familial cases. Following Bonferroni's correction for multiple tests, we found that the tumours with LOH of BRCA1 were still significantly associated with a high mitotic index (p = 0.0006) and a high degree of nuclear pleomorphism (p = 0.001). Int. J. Cancer 88:204-208, 2000, (C) 2000 Wiley-Liss, Inc.

Type:Article
Title:Association between loss of heterozygosity of BRCA1 and BRCA2 and morphological attributes of sporadic breast cancer
Keywords:COMPARATIVE GENOMIC HYBRIDIZATION, MULTIFACTORIAL ANALYSIS, HISTOLOGICAL GRADE, CARCINOMAS, MUTATIONS, GENE, EXPRESSION, RAD51
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health Care > CHIME

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