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Published on: July 25, 2020
Topoisomerase expression and amplification in solid tumours: Analysis of 24,262 patients
Gregory M Heestand1, Maria Schwaederle1, Zoran Gatalica2
1Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, 3855 Health Sciences Drive, La Jolla, CA 92093, USA.
Background:
Topoisomerase I (TOPO1) and topoisomerase IIα (TOP2A) are specific targets of multiple chemotherapy drugs. Increased expression of TOPO1 protein and amplification of the TOP2A gene have been associated with treatment response in colorectal and breast cancers, respectively. TOPO1 and TOP2A may be potential therapeutic targets in other malignancies as well.
Summary Of Methods:
We analysed TOPO1 protein expression and TOP2A gene amplification in patients (n = 24,262 specimens) with diverse cancers. Since HER2 and TOP2A co-amplification have been investigated for predictive value regarding anthracycline benefit, we analysed specimens for HER2 amplification as well.
Results:
Overexpressed TOPO1 protein was present in 51% of the tumours. Four percent of the tumours had TOP2A amplification, with gallbladder tumours and gastroesophageal/oesophageal tumours having rates over 10%. Overall, 4903 specimens were assessed for both TOP2A and HER2 amplification; 129 (2.6%) had co-amplification. High rates (>40%) of HER2 amplification were seen in patients with TOP2A amplification in breast, ovarian, gastroesophageal/oesophageal and pancreatic cancer.
Conclusion:
Our data indicate that increased TOPO1 expression and TOP2A amplification, as well as HER2 co-alterations, are present in multiple malignancies. The implications of these observations regarding sensitivity to chemotherapy not traditionally administered to these tumour types merits investigation.
Insights
Topoisomerase I (TOPO1) and topoisomerase IIα (TOP2A) are frequently overexpressed or amplified in various cancers. These findings suggest TOPO1 and TOP2A, along with HER2 alterations, may guide novel chemotherapy strategies in diverse malignancies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Topoisomerase I (TOPO1) and topoisomerase IIα (TOP2A) are crucial enzymes targeted by chemotherapy.
- Increased TOPO1 expression and TOP2A gene amplification are linked to treatment response in colorectal and breast cancers.
- These enzymes represent potential therapeutic targets across various cancer types.
Purpose of the Study:
- To analyze TOPO1 protein expression and TOP2A gene amplification in a large cohort of diverse cancer patients.
- To investigate the co-amplification of HER2 and TOP2A for their predictive value in cancer treatment.
Main Methods:
- Analysis of TOPO1 protein expression and TOP2A gene amplification in 24,262 diverse cancer specimens.
- Assessment of HER2 amplification in conjunction with TOP2A amplification in 4903 specimens.
Main Results:
- Overexpressed TOPO1 protein was found in 51% of tumors.
- TOP2A amplification occurred in 4% of tumors, notably higher in gallbladder and gastroesophageal/esophageal cancers (>10%).
- Co-amplification of TOP2A and HER2 was observed in 2.6% of assessed specimens, with high rates in breast, ovarian, gastroesophageal/esophageal, and pancreatic cancers.
Conclusions:
- Increased TOPO1 expression and TOP2A amplification are prevalent in multiple malignancies.
- Co-alterations involving TOPO1, TOP2A, and HER2 are significant findings across diverse cancers.
- Further research is warranted to explore the implications of these alterations for chemotherapy sensitivity in non-traditional tumor types.
