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Updated: Aug 14, 2026
Detection of a CDH1 Rare Transcript Variant in Fresh-frozen Gastric Cancer Tissues by Chip-based Digital PCR
Published on: February 5, 2018
CGH, cDNA and tissue microarray analyses implicate FGFR2 amplification in a small subset of breast tumors
M Heiskanen1, J Kononen, M Bärlund
1Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive MSC 4470, Room 4A15, Bethesda, MD 20892-4470, USA. mervi@cgen.com
Abstract:
Multiple regions of the genome are often amplified during breast cancer development and progression, as evidenced in a number of published studies by comparative genomic hybridization (CGH). However, only relatively few target genes for such amplifications have been identified. Here, we indicate how small-scale commercially available cDNA and CGH microarray formats combined with the tissue microarray technology enable rapid identification of putative amplification target genes as well as analysis of their clinical significance. According to CGH, the SUM-52 breast cancer cell line harbors several high-level DNA amplification sites, including the 10q26 chromosomal region where the fibroblast growth factor receptor 2 (FGFR2) gene has been localized. High level amplification of FGFR2 in SUM-52 was identified using CGH analysis on a microarray of BAC clones. A cDNA microarray survey of 588 genes showed >40-fold overexpression of FGFR2. Finally, a tissue microarray based FISH analysis of 750 uncultured primary breast cancers demonstrated in vivo amplification of the FGFR2 gene in about 1% of the tumors. In conclusion, three consecutive microarray (CGH, cDNA and tissue) experiments revealed high-level amplification and overexpression of the FGFR2 in a breast cancer cell line, but only a low frequency of involvement in primary breast tumors. Applied to a genomic scale with larger arrays, this strategy should facilitate identification of the most important target genes for cytogenetic rearrangements, such as DNA amplification sites detected by conventional CGH. Figures on http://www.esacp.org/acp/2001/22-4/heiskanen.htm
Insights
This study identifies fibroblast growth factor receptor 2 (FGFR2) amplification and overexpression in breast cancer cell lines using microarray techniques. While FGFR2 was highly amplified in cell lines, its amplification occurred in only 1% of primary breast tumors.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Oncology
Background:
- Genomic amplifications are common in breast cancer, but target genes are often unidentified.
- Comparative genomic hybridization (CGH) has identified amplification sites, yet specific gene targets remain elusive.
Purpose of the Study:
- To develop and apply a microarray-based strategy for rapid identification of amplification target genes in breast cancer.
- To analyze the clinical significance of identified amplification target genes.
Main Methods:
- Utilized comparative genomic hybridization (CGH) microarray to identify DNA amplification sites in breast cancer cell lines.
- Employed cDNA microarray to assess gene expression levels, specifically for fibroblast growth factor receptor 2 (FGFR2).
- Applied tissue microarray and fluorescence in situ hybridization (FISH) to evaluate FGFR2 amplification in primary breast tumors.
Main Results:
- The SUM-52 breast cancer cell line showed high-level DNA amplification at the 10q26 region, including the FGFR2 gene.
- FGFR2 was overexpressed >40-fold in the SUM-52 cell line, confirmed by cDNA microarray.
- In vivo amplification of FGFR2 was detected in approximately 1% of 750 primary breast tumors via tissue microarray FISH analysis.
Conclusions:
- A combined CGH, cDNA, and tissue microarray approach effectively identified high-level amplification and overexpression of FGFR2 in a breast cancer cell line.
- FGFR2 amplification is infrequent in primary breast tumors despite its high prevalence in certain cell lines.
- This strategy holds promise for identifying key target genes in cytogenetic rearrangements on a larger genomic scale.
