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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
Summary
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.
