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

Autor: Kümler I; Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark., Balslev E; Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev, Denmark., Poulsen TS; Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev, Denmark., Nielsen SL; Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Nygård SB; Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Rømer MU; Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Glostrup, Denmark., Christensen IJ; The Finsen Laboratory, Rigshospitalet and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Denmark., Høgdall E; Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev, Denmark., Moreira J; Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Nielsen DL; Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark., Brünner N; Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Stenvang J; Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2015 Oct 15; Vol. 137 (8), pp. 2000-6. Date of Electronic Publication: 2015 Apr 27.
DOI: 10.1002/ijc.29556
Abstrakt: 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.
(© 2015 UICC.)
Databáze: MEDLINE
Externí odkaz: