TOP2A
HGNC:11989 MIM.126430 17q21-q22 Enterz:7153
Definition: TOP2A gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription.
Function
This nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication.
TOP2A catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another, thus altering the topology of DNA.
Two forms of this enzyme exist as likely products of a gene duplication event.
The gene encoding this form, alpha (TOP2A), is localized to chromosome 17 and the beta gene (TOP2B) is localized to chromosome 3.
Pathology
Topoisomerase IIalpha (topoIIalpha), located at chromosome 17q21-22, is considered a major mediator of cell proliferation and DNA replication.
TopoIIalpha expression is associated with histologically aggressive subtypes and shortened survival in salivary gland carcinomas. (#19250538#)
- Furthermore, it may provide useful prognostic information and suggests the potential efficacy of topoIIalpha-targeting therapy in patients with salivary gland carcinoma.
- Salivary gland carcinomas are relatively uncommon heterogeneous malignancies characterized by locoregional invasion and distant metastasis.
The gene encoding this enzyme functions as the target for several anticancer agents and a variety of mutations in this gene have been associated with the development of drug resistance.
Reduced activity of this enzyme may also play a role in ataxia-telangiectasia.
Topoisomerase IIalpha gene amplification in gastric carcinomas (#16949920#)
ProEx C
BD ProEx C (ProEx C) is a recently developed immunocytochemical assay that targets the expression of topoisomerase II-alpha (TOP2A) and minichromosome maintenance protein-2 (MCM2), 2 genes shown to be overexpressed in cervical cancers.
ProEx C is a reliable marker for high-grade CIN that can be applied to tissue sections to confirm the diagnosis of high-grade CIN and to triage cases of atypical squamous metaplasia.
ProEx C may also have a potential role in triaging patients with low-grade CIN.
ProEx C expression patterns are similar to those for p16 and Ki67 with most discrepancies occurring in the CIN I category.
ProEx C is a useful proliferation marker for high-grade VIN analogous to the staining patterns reported in high-grade cervical intraepithelial neoplasia. (#20697251#)
See also
topoisomerase 1 (TOP1)
Links
Open References
Differential expression of topoisomerase IIalpha protein in salivary gland carcinomas: histogenetic and prognostic implications. Maruya S, Shirasaki T, Nagaki T, Kakehata S, Kurotaki H, Mizukami H, Shinkawa H. BMC Cancer. 2009 Feb 27;9:72. PMID: #19250538# [Free]
References
Immunohistochemical Patterns of ProEx C in Vulvar Squamous Lesions: Detection of Overexpression of MCM2 and TOP2A. Chen H, Gonzalez JL, Brennick JB, Liu M, Yan S. Am J Surg Pathol. 2010 Sep;34(9):1250-7. PMID: #20697251#
Evaluation of p16INK4a, minichromosome maintenance protein 2, DNA topoisomerase IIalpha, ProEX C, and p16INK4a/ProEX C in cervical squamous intraepithelial lesions. Shi J, Liu H, Wilkerson M, Huang Y, Meschter S, Dupree W, Schuerch C, Lin F. Hum Pathol. 2007 Sep;38(9):1335-44. PMID: #17512033#
Topoisomerase IIalpha gene amplification in gastric carcinomas: correlation with the HER2 gene. An immunohistochemical, immunoblotting, and multicolor fluorescence in situ hybridization study. Kanta SY, Yamane T, Dobashi Y, Mitsui F, Kono K, Ooi A. Hum Pathol. 2006 Oct;37(10):1333-43. PMID: #16949920#
The incidence of topoisomerase II-alpha genomic alterations in adenocarcinoma of the breast and their relationship to human epidermal growth factor receptor-2 gene amplification: a fluorescence in situ hybridization study. Hicks DG, Yoder BJ, Pettay J, Swain E, Tarr S, Hartke M, Skacel M, Crowe JP, Budd GT, Tubbs RR. Hum Pathol. 2005 Apr;36(4):348-56.PMID: #15891995#
Immunohistochemical study of DNA topoisomerase I, DNA topoisomerase II alpha, p53, and Ki-67 in oral preneoplastic lesions and oral squamous cell carcinomas. Hafian H, Venteo L, Sukhanova A, Nabiev I, Lefevre B, Pluot M. Hum Pathol. 2004 Jun;35(6):745-51. PMID: #15188142#
Topoisomerase IIalpha expression in ductal carcinoma in situ of the breast: a preliminary study. Shpitz B, Bomstein Y, Zehavi T, Bernheim J, Liverant S, Kaufman Z, Buklan G, Klein E. Hum Pathol. 2000 Oct;31(10):1249-54. PMID: #11070118#
Expression of DNA toposiomerase I and DNA topoisomerase II-alpha in testicular seminomas. Coleman LW, Perkins SL, Bronstein IB, Holden JA. Hum Pathol. 2000 Jun;31(6):728-33. PMID: #10872667#
DNA topoisomerase expression in tumors—a novel target for chemotherapy. Rubin EH. Hum Pathol. 2000 Jun;31(6):631-2. PMID: #10872653#