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. 2022 Jun 27;14(13):3148. doi: 10.3390/cancers14133148

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Schematic representation of the human TOP2α gene, TOP2α/90 mRNA, and TOP2α/90 protein. (A) The human TOP2α gene comprises 35 exons and spans ~35 kb. (B) When Intron 19 IPA occurs, the predominate TOP2α mRNA transcript is 2762 nucleotides long. (C) This mRNA transcript encodes a TOP2α isoform of 786 aa, denoted TOP2α/90. The truncated TOP2α isoform is missing the entire C-terminus (770 aa) present in TOP2α/170 and lacks the active site Tyr805. The TOP2α/90 isoform cannot form DNA covalent cleavage complexes and drug resistance occurs due to decreased drug-induced DNA damage, and cytotoxicity.