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 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...

Full description

Saved in:
Bibliographic Details
Main Authors: Mervi Heiskanen, Juha Kononen, Maarit Bärlund, Joachim Torhorst, Guido Sauter, Anne Kallioniemi, Olli Kallioniemi
Format: Article
Language:English
Published: Wiley 2001-01-01
Series:Analytical Cellular Pathology
Online Access:http://dx.doi.org/10.1155/2001/981218
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832566930062442496
author Mervi Heiskanen
Juha Kononen
Maarit Bärlund
Joachim Torhorst
Guido Sauter
Anne Kallioniemi
Olli Kallioniemi
author_facet Mervi Heiskanen
Juha Kononen
Maarit Bärlund
Joachim Torhorst
Guido Sauter
Anne Kallioniemi
Olli Kallioniemi
author_sort Mervi Heiskanen
collection DOAJ
description 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
format Article
id doaj-art-ecb7ac45e26341738d534206107b7958
institution Kabale University
issn 0921-8912
1878-3651
language English
publishDate 2001-01-01
publisher Wiley
record_format Article
series Analytical Cellular Pathology
spelling doaj-art-ecb7ac45e26341738d534206107b79582025-02-03T01:02:51ZengWileyAnalytical Cellular Pathology0921-89121878-36512001-01-0122422923410.1155/2001/981218CGH, cDNA and Tissue Microarray Analyses Implicate FGFR2 Amplification in a Small Subset of Breast TumorsMervi Heiskanen0Juha Kononen1Maarit Bärlund2Joachim Torhorst3Guido Sauter4Anne Kallioniemi5Olli Kallioniemi6Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive MSC 4470, Room 4A15, Bethesda, MD 20892‐4470, USACancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive MSC 4470, Room 4A15, Bethesda, MD 20892‐4470, USALaboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, 33521 Tampere, FinlandInstitute of Pathology, University of Basel, SwitzerlandInstitute of Pathology, University of Basel, SwitzerlandCancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive MSC 4470, Room 4A15, Bethesda, MD 20892‐4470, USACancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive MSC 4470, Room 4A15, Bethesda, MD 20892‐4470, USAMultiple 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.htmhttp://dx.doi.org/10.1155/2001/981218
spellingShingle Mervi Heiskanen
Juha Kononen
Maarit Bärlund
Joachim Torhorst
Guido Sauter
Anne Kallioniemi
Olli Kallioniemi
CGH, cDNA and Tissue Microarray Analyses Implicate FGFR2 Amplification in a Small Subset of Breast Tumors
Analytical Cellular Pathology
title CGH, cDNA and Tissue Microarray Analyses Implicate FGFR2 Amplification in a Small Subset of Breast Tumors
title_full CGH, cDNA and Tissue Microarray Analyses Implicate FGFR2 Amplification in a Small Subset of Breast Tumors
title_fullStr CGH, cDNA and Tissue Microarray Analyses Implicate FGFR2 Amplification in a Small Subset of Breast Tumors
title_full_unstemmed CGH, cDNA and Tissue Microarray Analyses Implicate FGFR2 Amplification in a Small Subset of Breast Tumors
title_short CGH, cDNA and Tissue Microarray Analyses Implicate FGFR2 Amplification in a Small Subset of Breast Tumors
title_sort cgh cdna and tissue microarray analyses implicate fgfr2 amplification in a small subset of breast tumors
url http://dx.doi.org/10.1155/2001/981218
work_keys_str_mv AT merviheiskanen cghcdnaandtissuemicroarrayanalysesimplicatefgfr2amplificationinasmallsubsetofbreasttumors
AT juhakononen cghcdnaandtissuemicroarrayanalysesimplicatefgfr2amplificationinasmallsubsetofbreasttumors
AT maaritbarlund cghcdnaandtissuemicroarrayanalysesimplicatefgfr2amplificationinasmallsubsetofbreasttumors
AT joachimtorhorst cghcdnaandtissuemicroarrayanalysesimplicatefgfr2amplificationinasmallsubsetofbreasttumors
AT guidosauter cghcdnaandtissuemicroarrayanalysesimplicatefgfr2amplificationinasmallsubsetofbreasttumors
AT annekallioniemi cghcdnaandtissuemicroarrayanalysesimplicatefgfr2amplificationinasmallsubsetofbreasttumors
AT ollikallioniemi cghcdnaandtissuemicroarrayanalysesimplicatefgfr2amplificationinasmallsubsetofbreasttumors