PMID- 19945923
OWN - NLM
STAT- MEDLINE
DCOM- 20100616
LR  - 20211020
IS  - 1878-0261 (Electronic)
IS  - 1574-7891 (Print)
IS  - 1574-7891 (Linking)
VI  - 4
IP  - 2
DP  - 2010 Apr
TI  - Aberrations of ERBB2 and TOP2A genes in breast cancer.
PG  - 161-8
LID - 10.1016/j.molonc.2009.11.001 [doi]
AB  - 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.
CI  - Copyright 2009 Federation of European Biochemical Societies. Published by 
      Elsevier B.V. All rights reserved.
FAU - Nielsen, Kirsten Vang
AU  - Nielsen KV
AD  - Dako A/S, Glostrup, Denmark. kirsten.vang@dako.com
FAU - Muller, Sven
AU  - Muller S
FAU - Moller, Susanne
AU  - Moller S
FAU - Schonau, Andreas
AU  - Schonau A
FAU - Balslev, Eva
AU  - Balslev E
FAU - Knoop, Ann S
AU  - Knoop AS
FAU - Ejlertsen, Bent
AU  - Ejlertsen B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091118
PL  - United States
TA  - Mol Oncol
JT  - Molecular oncology
JID - 101308230
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Poly-ADP-Ribose Binding Proteins)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
RN  - EC 5.99.1.3 (TOP2A protein, human)
SB  - IM
MH  - Antigens, Neoplasm/*genetics
MH  - Biomarkers, Tumor/genetics
MH  - Breast Neoplasms/*genetics/pathology
MH  - Cell Line, Tumor
MH  - Chromosomes, Human, Pair 17
MH  - DNA Topoisomerases, Type II/*genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Female
MH  - *Gene Amplification
MH  - Gene Deletion
MH  - Gene Dosage
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Metaphase
MH  - Poly-ADP-Ribose Binding Proteins
MH  - Receptor, ErbB-2/*genetics
PMC - PMC5527893
EDAT- 2009/12/01 06:00
MHDA- 2010/06/17 06:00
PMCR- 2010/04/01
CRDT- 2009/12/01 06:00
PHST- 2009/09/02 00:00 [received]
PHST- 2009/11/10 00:00 [revised]
PHST- 2009/11/11 00:00 [accepted]
PHST- 2009/12/01 06:00 [entrez]
PHST- 2009/12/01 06:00 [pubmed]
PHST- 2010/06/17 06:00 [medline]
PHST- 2010/04/01 00:00 [pmc-release]
AID - S1574-7891(09)00138-0 [pii]
AID - MOL2201042161 [pii]
AID - 10.1016/j.molonc.2009.11.001 [doi]
PST - ppublish
SO  - Mol Oncol. 2010 Apr;4(2):161-8. doi: 10.1016/j.molonc.2009.11.001. Epub 2009 Nov 
      18.