Topoisomerase-1 gene copy aberrations are frequent in patients with breast cancer

Iben Kümler, Eva Balslev, Tim Svenstrup Poulsen, Signe Lykke Nielsen, Sune Boris Nygård, Maria Unni Rømer, Ib Jarle Christensen, Estrid Vilma Solyom Høgdall, José Moreira, Dorte Lisbet Nielsen, Nils Brünner, Jan Stenvang

15 Citationer (Scopus)

Abstract

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 ∼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.

OriginalsprogEngelsk
TidsskriftInternational Journal of Cancer
Vol/bind137
Udgave nummer8
Sider (fra-til)2000-6
Antal sider7
ISSN1065-7541
DOI
StatusUdgivet - 15 okt. 2015

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