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Copy number changes in TOP2A have frequently been linked to ERBB2 (HER2) amplified breast cancers. To study this relationship, copy number changes of ERBB2 and TOP2A were investigated by fluorescence in situ hybridization (FISH) in two cell lines; one characterized by having amplification of both genes and the other by having amplification of ERBB2 and deletion of TOP2A. The characteristics are compared to findings on paired ERBB2 and TOP2A data from 649 patients with invasive breast cancer from a previously published biomarker study. The physical localization of FISH signals in metaphase spreads from cell lines showed that simultaneous amplification is not a simple co-amplification of a whole amplicon containing both genes. Most gene signals are translocated to abnormal marker chromosomes. ERBB2 genes but not TOP2A genes are present in tandem amplicons, leading to a higher ERBB2 ratio. This observation was confirmed by patient FISH data: among 276 (43% of all patients) abnormal tumors, 67% had different ERBB2 and TOP2A status. ERBB2 amplification with normal TOP2A status was found in 36% of the abnormal tumors (15% of all patients). Simultaneous amplification of both genes was found in 28% of the abnormal tumors (12% of all patients) while TOP2A deletion and ERBB2 amplification was observed in 16% of the abnormal cases (8% of all patients). A small number of tumors had TOP2A amplification (4%) or deletion (6%) without simultaneous changes of the ERBB2 gene. ERBB2 deletion was also observed (5%) but only in tumors with simultaneous TOP2A deletion. The average gene/reference ratio was significantly different: 5.0 for TOP2A but 7.2 for ERBB2 in the amplified tumors (P<0.01). Amplification of the two genes may be caused by different mechanisms, leading to higher level of amplification for ERBB2 compared to TOP2A. In the majority of breast cancer patients, simultaneous aberration of ERBB2 and TOP2A is not explained by simple co-amplification.
Kirsten Vang Nielsen, and
Sven Müller, and
Susanne Møller, and
Andreas Schønau, and
Eva Balslev, and
Ann S Knoop, and
Bent Ejlertsen
May 2004,
Genes, chromosomes & cancer,
Kirsten Vang Nielsen, and
Sven Müller, and
Susanne Møller, and
Andreas Schønau, and
Eva Balslev, and
Ann S Knoop, and
Bent Ejlertsen
January 2017,
Medicine,
Kirsten Vang Nielsen, and
Sven Müller, and
Susanne Møller, and
Andreas Schønau, and
Eva Balslev, and
Ann S Knoop, and
Bent Ejlertsen
January 2004,
Acta oncologica (Stockholm, Sweden),
Kirsten Vang Nielsen, and
Sven Müller, and
Susanne Møller, and
Andreas Schønau, and
Eva Balslev, and
Ann S Knoop, and
Bent Ejlertsen
January 2003,
Anticancer research,
Kirsten Vang Nielsen, and
Sven Müller, and
Susanne Møller, and
Andreas Schønau, and
Eva Balslev, and
Ann S Knoop, and
Bent Ejlertsen
November 2006,
Current cancer drug targets,
Kirsten Vang Nielsen, and
Sven Müller, and
Susanne Møller, and
Andreas Schønau, and
Eva Balslev, and
Ann S Knoop, and
Bent Ejlertsen
January 2006,
Neoplasma,
Kirsten Vang Nielsen, and
Sven Müller, and
Susanne Møller, and
Andreas Schønau, and
Eva Balslev, and
Ann S Knoop, and
Bent Ejlertsen
June 2001,
Cancer genetics and cytogenetics,
Kirsten Vang Nielsen, and
Sven Müller, and
Susanne Møller, and
Andreas Schønau, and
Eva Balslev, and
Ann S Knoop, and
Bent Ejlertsen
February 2022,
Diagnostics (Basel, Switzerland),
Kirsten Vang Nielsen, and
Sven Müller, and
Susanne Møller, and
Andreas Schønau, and
Eva Balslev, and
Ann S Knoop, and
Bent Ejlertsen
March 2006,
Endocrine-related cancer,
Kirsten Vang Nielsen, and
Sven Müller, and
Susanne Møller, and
Andreas Schønau, and
Eva Balslev, and
Ann S Knoop, and
Bent Ejlertsen
May 2014,
Journal of clinical pathology,
