INCREASED COPY NUMBER AT 20Q13 IN BREAST-CANCER - DEFINING THE CRITICAL REGION AND EXCLUSION OF CANDIDATE GENES

Studies by comparative genomic hybridization have indicated that a maj or new locus for DNA amplification in breast cancer is 20q13 and sugge sted that this genetic event is associated with aggressive clinical be havior. We used interphase fluorescence in situ hybridization with ano nymous cosmid probes and gene-specific P1 clones to determine the mini mal common region of increased copy number and to study involvement of known genes at 20q13. Based on high-level copy number increases (3 to 10-fold) found with one or more probes in 5 of 14 (35%) breast cancer cell lines and in 3 of 36 (8%) primary tumors, the critical region wa s narrowed to similar to 1.5 megabases at 20q13.2 defined by fractiona l length pter values 0.81-0.84. Previously known genes were excluded a s candidates, implying that this chromosomal region harbors a novel on cogene that contributes to the malignant progression of breast cancer.