OBJECTIVE: A positive relationship between topoisomerase-1 (TOP1) protein and sensitivity toward the TOP1 inhibitor irinotecan has been reported in patients with metastatic colorectal cancer (mCRC). In this study, we analyzed TOP1 gene copy number variation in tumor tissue from CRC patients and CRC cell lines with different sensitivities to the TOP1 inhibitor SN-38 and oxaliplatin. MATERIAL AND METHODS: A TOP1 gene probe with a chromosome 20 centromere (CEN-20) reference probe was applied on normal mucosa and on tumor tissue from 50 stage III CRC patients. Additionally, associations between TOP1/CEN-20 ratio and in vitro sensitivity to SN-38 (irinotecan) and oxaliplatin were tested on 10 CRC cell lines. Results. In the malignant epithelium, 84% of the samples demonstrated an increased TOP1 gene copy number and 64% had an increased TOP1/CEN-20 ratio compared with the non-affected mucosa. Sixteen (32%) of the tumors had a ratio of ≥ 1.5 and 9 (18%) of these had a ratio of ≥ 2.0. A positive association was observed between the TOP1 gene copy number and the TOP1/CEN-20 ratio and in vitro sensitivity toward SN-38, but not toward oxaliplatin. CONCLUSIONS: A large fraction of the clinical samples demonstrated increased TOP1 gene copy number and increased TOP1/CEN-20 ratio. The cell line study suggested an association between TOP1 gene copy number or TOP1/CEN-20 ratio and sensitivity to irinotecan but not oxaliplatin.
OBJECTIVE: A positive relationship between topoisomerase-1 (TOP1) protein and sensitivity toward the TOP1 inhibitor irinotecan has been reported in patients with metastatic colorectal cancer (mCRC). In this study, we analyzed TOP1 gene copy number variation in tumor tissue from CRC patients and CRC cell lines with different sensitivities to the TOP1 inhibitor SN-38 and oxaliplatin. MATERIAL AND METHODS: A TOP1 gene probe with a chromosome 20 centromere (CEN-20) reference probe was applied on normal mucosa and on tumor tissue from 50 stage III CRC patients. Additionally, associations between TOP1/CEN-20 ratio and in vitro sensitivity to SN-38 (irinotecan) and oxaliplatin were tested on 10 CRC cell lines. Results. In the malignant epithelium, 84% of the samples demonstrated an increased TOP1 gene copy number and 64% had an increased TOP1/CEN-20 ratio compared with the non-affected mucosa. Sixteen (32%) of the tumors had a ratio of ≥ 1.5 and 9 (18%) of these had a ratio of ≥ 2.0. A positive association was observed between the TOP1 gene copy number and the TOP1/CEN-20 ratio and in vitro sensitivity toward SN-38, but not toward oxaliplatin. CONCLUSIONS: A large fraction of the clinical samples demonstrated increased TOP1 gene copy number and increased TOP1/CEN-20 ratio. The cell line study suggested an association between TOP1 gene copy number or TOP1/CEN-20 ratio and sensitivity to irinotecan but not oxaliplatin.
Authors: Maria Unni Rømer; Sune Boris Nygård; Ib Jarle Christensen; Signe Lykke Nielsen; Kirsten Vang Nielsen; Sven Müller; David Hersi Smith; Ben Vainer; Hans Jørgen Nielsen; Nils Brünner Journal: Mol Oncol Date: 2012-10-11 Impact factor: 6.603
Authors: Jan Stenvang; Iben Kümler; Sune Boris Nygård; David Hersi Smith; Dorte Nielsen; Nils Brünner; José M A Moreira Journal: Front Oncol Date: 2013-12-25 Impact factor: 6.244
Authors: Manish R Sharma; James T Auman; Nirali M Patel; Juneko E Grilley-Olson; Xiaobei Zhao; Stergios J Moschos; Joel S Parker; Xiaoying Yin; Michele C Hayward; Blase N Polite; Elena Marangon; Bianca Posocco; Giuseppe Toffoli; D Neil Hayes; Federico Innocenti Journal: JCO Precis Oncol Date: 2017-04-27
Authors: David Hersi Smith; Ib Jarle Christensen; Niels Frank Jensen; Bo Markussen; Maria Unni Rømer; Sune Boris Nygård; Sven Müller; Hans Jørgen Nielsen; Nils Brünner; Kirsten Vang Nielsen Journal: PLoS One Date: 2013-04-05 Impact factor: 3.240
Authors: Niels Frank Jensen; Keli Agama; Amit Roy; David Hersi Smith; Thomas D Pfister; Maria Unni Rømer; Hong-Liang Zhang; James H Doroshow; Birgitta R Knudsen; Jan Stenvang; Nils Brünner; Yves Pommier Journal: J Exp Clin Cancer Res Date: 2016-03-31
Authors: Haatisha Jandu; Kristina Aluzaite; Louise Fogh; Sebastian Wingaard Thrane; Julie B Noer; Joanna Proszek; Khoa Nguyen Do; Stine Ninel Hansen; Britt Damsgaard; Signe Lykke Nielsen; Magnus Stougaard; Birgitta R Knudsen; José Moreira; Petra Hamerlik; Madhavsai Gajjar; Marcel Smid; John Martens; John Foekens; Yves Pommier; Nils Brünner; Anne-Sofie Schrohl; Jan Stenvang Journal: BMC Cancer Date: 2016-01-22 Impact factor: 4.430