TOP2A
Overview
TOP2A encodes DNA topoisomerase II alpha, an enzyme essential for DNA replication, transcription, and chromosome segregation. TOP2A amplification and/or overexpression is observed across multiple cancer types and serves as a predictive biomarker for sensitivity to topoisomerase II inhibitors (e.g., anthracyclines, etoposide, irinotecan). Elevated TOP2A expression is associated with high proliferative activity.
Alterations observed in the corpus
- TOP2A amplification with high expression identified in neuroendocrine neoplasm patient PN4 (a PanNET) by whole-genome/transcriptome analysis; supported irinotecan recommendation within a WGTA-guided precision oncology cohort PMID:24326773
Cancer types (linked)
- Pancreatic neuroendocrine neoplasm (PanNET): TOP2A amplification and high expression observed in PN4; used to guide topoisomerase II inhibitor (irinotecan) therapy selection PMID:24326773
Co-occurrence and mutual exclusivity
- TOP2A amplification in PN4 co-occurred with biallelic MSH6/MLH1 loss-of-function and high TMB (~11 mut/Mb); the patient was classified as MSI-low despite dMMR PMID:24326773
Therapeutic relevance
- TOP2A amplification/overexpression supports use of topoisomerase II inhibitors (irinotecan) in NENs; this approach was applied in patient PN4 within a precision oncology program PMID:24326773
Open questions
- The prognostic and predictive significance of TOP2A amplification specifically in NENs versus other cancer types requires further prospective study.
Sources
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