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Topoisomerase II α gene ( TOP2A ) amplification and deletion in cancer – more common than anticipated
Author(s) -
Järvinen T. A. H.,
Liu E. T.
Publication year - 2003
Publication title -
cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.512
H-Index - 48
eISSN - 1365-2303
pISSN - 0956-5507
DOI - 10.1046/j.0956-5507.2003.00105.x
Subject(s) - amplicon , gene duplication , locus (genetics) , oncogene , gene , biology , gene dosage , cancer research , cancer , breast cancer , topoisomerase , genetics , polymerase chain reaction , microbiology and biotechnology , dna , gene expression , cell cycle
In solid tumours the predominant genetic mechanism for oncogene activation is through amplification of genes. The HER ‐ 2 (also known as ErbB 2 / c ‐ erbB 2 / HER ‐ 2 / neu ) oncogene is the most frequently amplified oncogene in breast cancer and is also commonly amplified in other forms of cancer. The HER ‐ 2 amplicon also contains other biologically relevant genes with altered copy numbers, among these genes is the topoisomerase IIα ( TOP 2 A ). TOP 2 A gene is located adjacent to the HER ‐ 2 oncogene at the chromosome location 17q12‐q21 and is either amplified or deleted, with equal frequency, in almost 90% of HER ‐ 2 amplified primary breast tumours. Recent data suggest that amplification and deletion of TOP 2 A may account for both sensitivity and resistance to topoII ‐inhibitor‐chemotherapy, depending on the specific genetic defect at the TOP 2 A locus. In this issue of the Cytopathology , Bofin et al . present preliminary evidence for high prevalance of TOP 2 A amplification and deletion not only in the HER‐ 2 amplified breast tumours, but also in the primary breast tumours without the HER‐ 2 amplification. This finding together with the concept that TOP 2 A gene amplification and deletion seem to account for both relative chemosensitivity and resistance to topoII‐inhibitor therapy further highlights the importance of screening for TOP 2 A gene copy number aberrations when topoII‐inhibitors are considered either alone or in combination of other chemotherapeutic drugs for the treatment of cancer patients.