ArticlePloS one2013
Mechanisms of topoisomerase I (TOP1) gene copy number increase in a stage III colorectal cancer patient cohort.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Integrated analysis of copy number variation and genome-wide expression profiling in colorectal cancer tissues.PloS one · 2014Trial
- RNA interacts with topoisomerase I to adjust DNA topology.Molecular cell · 2024Article
- Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome.Science advances · 2024Article
- Resistance to TOP-1 Inhibitors: Good Old Drugs Still Can Surprise Us.International journal of molecular sciences · 2023Review
- Hepatoid adenocarcinoma of the stomach: a unique subgroup with distinct clinicopathological and molecular features.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2019Article
- Topoisomerase I copy number alterations as biomarker for irinotecan efficacy in metastatic colorectal cancer.BMC cancer · 2017Article
- Article
- Characterization of DNA topoisomerase I in three SN-38 resistant human colon cancer cell lines reveals a new pair of resistance-associated mutations.Journal of experimental & clinical cancer research : CR · 2016Article
- Brain Delivery of Drug and MRI Contrast Agent: Detection and Quantitative Determination of Brain Deposition of CPT-Glu Using LC-MS/MS and Gd-DTPA Using Magnetic Resonance Imaging.Molecular pharmaceutics · 2016Article
- Pharmacologic resistance in colorectal cancer: a review.Therapeutic advances in medical oncology · 2016Review
- Topoisomerase-1 and -2A gene copy numbers are elevated in mismatch repair-proficient colorectal cancers.Molecular oncology · 2015Article
- Article
- Preferential potentiation of topoisomerase I poison cytotoxicity by PARP inhibition in S phase.British journal of cancer · 2014Article
- Measuring ERCC1 protein expression in cancer specimens: validation of a novel antibody.Scientific reports · 2014Article
- Topoisomerase I as a biomarker: detection of activity at the single molecule level.Sensors (Basel, Switzerland) · 2014Article
- Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development.Frontiers in oncology · 2013Review
- Alternative lengthening of telomeres: recurrent cytogenetic aberrations and chromosome stability under extreme telomere dysfunction.Neoplasia (New York, N.Y.) · 2013Article
- An explorative analysis of ERCC1-19q13 copy number aberrations in a chemonaive stage III colorectal cancer cohort.BMC cancer · 2013Article
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10 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundTopoisomerase I (Top1) is the target of Top1 inhibitor chemotherapy. The TOP1 gene, located at 20q12-q13.1, is frequently detected at elevated copy numbers in colorectal cancer (CRC). The present study explores the mechanism, frequency and prognostic impact of TOP1 gene aberrations in stage III CRC and how these can be detected by fluorescent in situ hybridization (FISH).
methodsNine CRC cell line metaphase spreads were analyzed by FISH with a TOP1 probe in combination with a reference probe covering either the centromeric region of chromosome 20 (CEN-20) or chromosome 2 (CEN-2). Tissue sections from 154 chemonaive stage III CRC patients, previously studied with TOP1/CEN-20, were analyzed with TOP1/CEN-2. Relationships between biomarker status and overall survival (OS), time to recurrence (TTR) in CRC and time to local recurrence (LR; rectal cancer only) were determined.
resultsTOP1 aberrations were observed in four cell line metaphases. In all cell lines CEN-2 was found to reflect chromosomal ploidy levels and therefore the TOP1/CEN-2 probe combination was selected to identify TOP1 gene gains (TOP1/CEN-2≥1.5). One hundred and three patients (68.2%) had TOP1 gain, of which 15 patients (14.6%) harbored an amplification (TOP1/CEN-20≥2.0). TOP1 gene gain did not have any association with clinical endpoints, whereas TOP1 amplification showed a non-significant trend towards longer TTR (multivariate HR: 0.50, p = 0.08). Once amplified cases were segregated from other cases of gene gain, non-amplified gene increases (TOP1/CEN-2≥1.5 and TOP1/CEN-20<2.0) showed a trend towards shorter TTR (univariate HR: 1.57, p = 0.07).
conclusionsTOP1 gene copy number increase occurs frequently in stage III CRC in a mechanism that often includes CEN-20. Using CEN-2 as a measurement for tumor ploidy levels, we were able to discriminate between different mechanisms of gene gain, which appeared to differ in prognostic impact. TOP1 FISH guidelines have been updated.
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