CGH, cDNA and tissue microarray analyses implicate FGFR2 amplification in a small subset of breast tumors

Multiple regions of the genome are often amplified during breast cancer dev elopment and progression, as evidenced in a number of published studies by comparative genomic hybridization (CGH). However, only relatively few targe t genes for such amplifications have been identified. Here, we indicate how small-scale commercially available cDNA and CGH microarray for-mats combin ed with the tissue microarray technology enable rapid identification of put ative amplification target genes as well as analysis of their clinical Sign ificance. According to CGH, the SUM-52 breast cancer cell line harbors seve ral high-level DNA amplification sites, including the 10q26 chromosomal reg ion where the fibroblast growth factor receptor 2 (FGFR2) gene has been loc alized. High level amplification of FGFR2 in SUM-52 was identified using CG H analysis on a microarray of BAC clones. A cDNA microarray survey of 588 g enes showed >40-fold overexpression of FGFR2. Finally, a tissue microarray based FISH analysis of 750 uncultured primary breast cancers demonstrated i n vivo amplification of the FGFR2 gene in about 1% of the tumors. In conclu sion, three consecutive microarray (CGH, cDNA and tissue) experiments revea led high-level amplification and overexpression of the FGFR2 in a breast ca ncer cell line, but only a low frequency of involvement in primary breast t umors. Applied to a genomic scale with larger arrays, this strategy should facilitate identification of the most important target genes for cytogeneti c rearrangements, such as DNA amplification sites detected by conventional CGH.