Topoisomerase-1 gene copy aberrations are frequent in patients with breast cancer
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Topoisomerase-1 gene copy aberrations are frequent in patients with breast cancer. / Kümler, Iben; Balslev, Eva; Poulsen, Tim S.; Nielsen, Signe Lykke; Nygård, Sune Boris; Rømer, Maria Unni; Christensen, Ib Jarle; Høgdall, Estrid; Moreira, José; Nielsen, Dorte Lisbet; Brünner, Nils; Stenvang, Jan.
In: International Journal of Cancer, Vol. 137, No. 8, 08.04.2015, p. 2000-2006.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Topoisomerase-1 gene copy aberrations are frequent in patients with breast cancer
AU - Kümler, Iben
AU - Balslev, Eva
AU - Poulsen, Tim S.
AU - Nielsen, Signe Lykke
AU - Nygård, Sune Boris
AU - Rømer, Maria Unni
AU - Christensen, Ib Jarle
AU - Høgdall, Estrid
AU - Moreira, José
AU - Nielsen, Dorte Lisbet
AU - Brünner, Nils
AU - Stenvang, Jan
N1 - © 2015 UICC.
PY - 2015/4/8
Y1 - 2015/4/8
N2 - Topoisomerase-1 (Top1) targeting drugs have shown promising efficacy in patients with metastatic breast cancer (BC). However, these drugs are rather toxic calling for development and validation of predictive biomarkers to increase the therapeutic index. As these drugs are targeting the Top1 protein, and since no validated anti-Top1 antibodies for immunohistochemistry have been reported, we raised the hypothesis that TOP1 gene amplifications may serve as a proxy for the Top1 protein and thereby a biomarker of response to treatment with Top1 inhibitors in BC. The aim was to determine the prevalence of TOP1 gene copy gain in BC. The prevalence of TOP1 gene copy gain was investigated by fluorescence in situ hybridization with a TOP1/CEN-20 probemix in normal breast tissue (N=100) and in tissue from patients with metastatic BC in a discovery (N=100) and a validation cohort (N=205). As amplification of 20q including CEN-20 is common in BC a TOP1/CEN-2 probemix was applied to the validation cohort. More than 30% of the patients had gene copy numbers of ≥ 4 and approximately 20% of the patients had TOP1/CEN-20 ratios ≥ 1.5. The CEN-2 probe did not add any information. Gain of the TOP1 gene appears to be common in BC making the gene a potential biomarker for response to treatment with Top1 inhibitors. As 20q amplification is a common finding in BC and as no other suitable reference gene has yet been identified, TOP1 copy number may be a more valid method of detecting gain than using a gene/centromere ratio. This article is protected by copyright. All rights reserved.
AB - Topoisomerase-1 (Top1) targeting drugs have shown promising efficacy in patients with metastatic breast cancer (BC). However, these drugs are rather toxic calling for development and validation of predictive biomarkers to increase the therapeutic index. As these drugs are targeting the Top1 protein, and since no validated anti-Top1 antibodies for immunohistochemistry have been reported, we raised the hypothesis that TOP1 gene amplifications may serve as a proxy for the Top1 protein and thereby a biomarker of response to treatment with Top1 inhibitors in BC. The aim was to determine the prevalence of TOP1 gene copy gain in BC. The prevalence of TOP1 gene copy gain was investigated by fluorescence in situ hybridization with a TOP1/CEN-20 probemix in normal breast tissue (N=100) and in tissue from patients with metastatic BC in a discovery (N=100) and a validation cohort (N=205). As amplification of 20q including CEN-20 is common in BC a TOP1/CEN-2 probemix was applied to the validation cohort. More than 30% of the patients had gene copy numbers of ≥ 4 and approximately 20% of the patients had TOP1/CEN-20 ratios ≥ 1.5. The CEN-2 probe did not add any information. Gain of the TOP1 gene appears to be common in BC making the gene a potential biomarker for response to treatment with Top1 inhibitors. As 20q amplification is a common finding in BC and as no other suitable reference gene has yet been identified, TOP1 copy number may be a more valid method of detecting gain than using a gene/centromere ratio. This article is protected by copyright. All rights reserved.
U2 - 10.1002/ijc.29556
DO - 10.1002/ijc.29556
M3 - Journal article
C2 - 25855483
VL - 137
SP - 2000
EP - 2006
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 8
ER -
ID: 135276395