GENOME-WIDE SEARCH FOR LOSS OF HETEROZYGOSITY SHOWS EXTENSIVE GENETICDIVERSITY OF HUMAN BREAST CARCINOMAS

Deletions of genomic regions involving tumor suppressor genes are thou ght to be important in the initiation and progression of breast cancer . We conducted a genome-wide search fur deleted regions in a series of 75 human breast carcinomas by studying the allelic patterns of 184 mi crosatellite markers distributed over all chromosomes and looking for loss of heterozygosity (LOH), We identified 56 regions of consistent L OH, Strikingly , every tumor had a different set of deletions. To stud y this complexity, we applied a phylogenetic-like type of analysis, Ea ch region was involved in a certain proportion of tumors, ranging from 20 to 62%; the most frequently involved regions were on chromosome ar ms 8p, 11q, 16q, and 17p, There was a correlation (P = 0.005) between the level of LOH and the size of the tumors, Tumors with a high revel of LOH were also highly proliferative and had a high mitotic index.