CONSORTIUM STUDY ON 1280 BREAST CARCINOMAS - ALLELIC LOSS ON CHROMOSOME-17 TARGETS SUBREGIONS ASSOCIATED WITH FAMILY HISTORY AND CLINICAL-PARAMETERS

The pattern of loss of heterozygosity (LOH) on chromosome 17 in human breast cancer is complicated and shows many different regions of loss. In an attempt to narrow down the relevant regions of LOH on chromosom e 17, we have studied the deletion pattern and its association with cl inical parameters in 1280 breast carcinoma-venous blood lymphocyte pai rs. In total, 42 different chromosome 17 loci were investigated, and b etween 25 and 625 cases were analyzed at each Locus, The frequency of LOB observed on the p arm was much higher than that observed on the q arm. The opposite effect was observed in 52 ovarian cancer cases inves tigated, with less LOH on 17p than on 17q. Patterns of loss consistent with interstitial and terminal deletions, as well as loss of either t he p or q arm or monosomy 17 were observed. To determine whether loss at particular loci may be associated with biological features of breas t tumors, clinical data including age of onset, family history of brea st cancer, tumor histopathology, tumor size, estrogen receptor (ER) st atus, and occurrence of lymph node or distant metastases were collecte d for each case. Overall, large-sized, ER-negative, lymph node-positiv e ductal tumors showed the highest frequencies of LOH with ER-negative and ductal tumors showing LOH for markers along the majority of the c hromosome. Eight regions of chromosome 17 appear to be associated with human breast cancel; two on 17p and six on 17q. These regions were no t necessarily in the areas exhibiting the highest frequencies of LOH h ut were defined by interstitial and terminal deletions in multiple ind ependent cases. Seven of these regions showed statistically significan t differences in LOH associated with clinical parameters, These data s trongly suggest that loci on chromosome 17 may determine aspects of tu mor presentation and disease behavior in human breast cancer anal pinp oint candidate tumor suppressor gene loci.