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 breast cancer, We have constructed a 2.8 Mb YAC contig of this region, centered on the human Fibroblast Growth Factor Receptor 1 (FGRF1) locus and encompassing the Adrenergic beta 3 Receptor (ADRB3) focus. A smaller centromeric YAC contig spanning 1.4 Mb was also assembled, and included the Ankyrin 1 (ANK1) and Tissue-type Plasminogen Activator (FLAT) genes, Results from mapping of the contigs showed physical linkage of the ADRB3 and FGFR1 genes, which were colocalized within the same YAC clone and separated by about 900 kb, FGFR1 being in centromeric position, It also showed physical linkage of ANK1 and FLAT genes, which appear to be separated by a maximum of 700 kb. In parallel, several loci were mapped according to their amplification status in a large panel of breast tumor samples. The overall amplification pattern suggested a continuous amplicon with a core around FGFR1. Data from both the detailed physical map and the amplification status allowed to establish the following gene order, from telomere to centromere: ADRB3-D8S105-FGFR1-ANK1-PLAT-POLB. The precise localization and YAC cloning of the core of the amplicon will allow to isolate a putative oncogene involved in mammary carcinogenesis.