CHARACTERIZATION OF THE REGION OF THE SHORT ARM OF CHROMOSOME-8 AMPLIFIED IN BREAST-CARCINOMA

Chromosomal region 8p11.2-p12 is consistently amplified in human breas t cancer, We have constructed a 2.8 Mb YAC contig of this region, cent ered on the human Fibroblast Growth Factor Receptor 1 (FGRF1) locus an d encompassing the Adrenergic beta 3 Receptor (ADRB3) focus. A smaller centromeric YAC contig spanning 1.4 Mb was also assembled, and includ ed the Ankyrin 1 (ANK1) and Tissue-type Plasminogen Activator (FLAT) g enes, Results from mapping of the contigs showed physical linkage of t he ADRB3 and FGFR1 genes, which were colocalized within the same YAC c lone and separated by about 900 kb, FGFR1 being in centromeric positio n, It also showed physical linkage of ANK1 and FLAT genes, which appea r to be separated by a maximum of 700 kb. In parallel, several loci we re mapped according to their amplification status in a large panel of breast tumor samples. The overall amplification pattern suggested a co ntinuous amplicon with a core around FGFR1. Data from both the detaile d physical map and the amplification status allowed to establish the f ollowing gene order, from telomere to centromere: ADRB3-D8S105-FGFR1-A NK1-PLAT-POLB. The precise localization and YAC cloning of the core of the amplicon will allow to isolate a putative oncogene involved in ma mmary carcinogenesis.