LOSS OF HETEROZYGOSITY OF BRCA1, BRCA2 AND ATM GENES IN SPORADIC INVASIVE DUCTAL BREAST-CARCINOMA

The present study was undertaken to analyse the loss: of heterozygosit y (LOH) of the three genes, BRCA1, BRCA2 and ATM, and their correlatio n to clinicopathological parameters in sporadic breast cancer. We stud ied 59 sets of invasive ductal carcinoma, compared to matched normal c ontrol DNA. Microsatellite markers intragenic to BRCA1 (D17S1323, D17S 1322, D17S855), BRCA2 (D13S1699. D13S1701, D13S1695) and ATM (D11S2179 ) were simultaneously used, in addition. I,ne marker telomeric to BRCA 2 (D13S1694) and four markers flanking ATM were analysed (D11S1816, D1 1S1819. D11S1294, D11S1818). Thirty-one per cent of the informative ca ses showed loss of heterozygosity for the BRCA1 gene, 22.8% for BRCA2? gene and 40% for ATM. LOH of BRCA1 correlated with high grade tumors (p=0.0005) and negative hormone receptors (p=0.01). LOH of ATM correla ted with higher grade (p=0.03) and a younger age at diagnosis (p=0.03) in our set of tumors. No correlations were detected between BRCA2 LOH and any of the analysed clinicopathological parameters. However. a co rrelation was detected between allelic loss of the D13S1694 marker, te lomeric to BRCA2, and larger tumor sizes: and negative estrogen recept ors, favoring the hypothesis of the presence of another putative tumor suppressor gene, telomeric to BRCA2. in the 13q12-q14 region. Only 11 tumors had LOH at more than one of the three genes, most of them (6/1 1) associated LOH of BRCA1 and ATM. One tumor only combined loss of th e three genes BRCA1, BRCA2 and ATM.