Aberrations of ERBB2 and TOP2A genes in breast cancer

Molecular Oncology - Tập 4 - Trang 161-168 - 2010
Kirsten Vang Nielsen1, Sven Müller1, Susanne Møller2, Andreas Schønau1, Eva Balslev3, Ann S. Knoop4, Bent Ejlertsen2,5
1Dako A/S, Glostrup, Denmark
2Danish Breast Cancer Cooperative Group (DBCG) Registry, Copenhagen, Denmark
3Department of Pathology, Herlev University Hospital, Herlev, Denmark
4Department of Oncology, Odense University Hospital, Odense, Denmark
5Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

Tóm tắt

AbstractCopy 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.

Tài liệu tham khảo

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Molecular Oncology

Tập 4

161-168

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