Topoisomerase-1 and -2A gene copy numbers are elevated in mismatch repair-proficient colorectal cancers

Molecular Oncology
Ida Marie Heeholm SønderstrupLene Riis

Abstract

Topoisomerase 1 (TOP1) and 2A (TOP2A) are potential predictive biomarkers for irinotecan and anthracycline treatment, respectively, in colorectal cancer (CRC), and we have recently reported a high frequency of gene gain of the TOP1 and TOP2A genes in CRC. Furthermore, Mismatch Repair (MMR) subtypes of CRC have been associated with benefit from adjuvant chemotherapy of primary CRC. Given the involvement of the topoisomerase enzymes in DNA replication and repair, we raised the hypothesis that an association may exist between TOP gene copy numbers and MMR proficiency/deficiency in CRC. Test cohort: FISH analysis with an in-house TOP1/CEN20 probe mix and a commercially available TOP2A/CEN17 (Dako, Glostrup, Denmark) probe mix was performed on archival formalin fixed paraffin embedded (FFPE) tissue samples from 18 patients with proficient MMR (pMMR) CRC and 18 patients with deficient MMR (dMMR) CRC. TOP1 and TOP2A gene copy numbers and their ratios per nucleus were correlated with MMR status using the Mann-Whitney test. Validation cohort: FFPE samples from 154 patients with primary stage III CRC (originally included in the RANX05 study) were classified according to MMR status by immunohistochemical analysis using validated antibodie...Continue Reading

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Citations

Mar 11, 2020·Frontiers in Genetics·Xiang DingHesheng Luo
May 3, 2020·Nature Communications·Jessica M Silva-FisherChristopher A Maher
Mar 31, 2021·Acta Oncologica·Line S TarpgaardPer Pfeiffer
Jun 3, 2021·International Journal of Environmental Research and Public Health·Abhijeet R PatilSourav Roy
Jun 3, 2021·International Journal of Environmental Research and Public Health·Urbashi BasnetSourav Roy

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