TOP2Agene copy number change in breast cancer

Abstract

AimsThe clinical significance of TOP2A as a prognostic marker has not been clarified. The aims of this study were to investigate the frequency of TOP2A copy number change; to correlate TOP2A with HER2 status, hormone receptor (HR) status and molecular subtype, and further to explore differences in breast cancer-specific survival according to TOP2A and HER2.MethodsIn this study, TOP2A, HER2 and chromosome 17 copy number were assessed in 670 cases of breast cancer using in situ hybridisation techniques. Gene to chromosome ratios ≥2 were classified as amplification. TOP2A deletion (gene to chromosome ratio ≤0.8) or monosomy (only one signal for both gene and chromosome in more than 75% of nuclei) were classified as gene loss.ResultsA strong association between TOP2A change and HR and HER2 status was found. During the first 5 years after diagnosis, the risk of death from breast cancer was significantly higher for cases with HER2 amplification irrespective of TOP2A status.ConclusionsTOP2A copy number change was strongly associated with HR and HER2 status and as a prognostic marker TOP2A is probably of limited value.

Amplification of HER2 and TOP2A and deletion of TOP2A genes in a series of Taiwanese breast cancer

“…[12,13,30] One study even reported that deleted cases had worse prognosis than amplified cases. [30] Our study demonstrates that TOP2A amplification is not a prognostic factor, which is consistent with the data of Engstrøm et al [14] The percentage of TOP2A deletion in this study is too low for analyzing the association with the clinical outcome.…”

“…The reported rate of TOP2A amplification and deletion in studies limited to HER2-positive cases is 35% to 50% and 13% to 42%, respectively. [24–26] The frequency of TOP2A deletion in studies including both HER2-positive and HER2-negative tumors is 3.7% to 17.0%, [6,10–14,27,28] and a similar frequency is reported for amplification. In the present study, 9.8% of TOP2A amplification is in line with the reported frequency by other studies, but 2.8% of TOP2A deletion is lower than that in other studies.…”

“…[12] In comparison, the prognostic value of TOP2A alteration has been reported in a limited number of studies. [13,14] …”

Frequency of chromosome 17 polysomy in relation to CEP17 copy number in a large breast cancer cohort

“…In our cohort, a gain of all markers except TOP2A was found in three cases. Considering the clearly confirmed TOP2A deletion in HER2 positive cases (Engstrom et al, ; Almeida et al, ), we assume that these cases concern a polysomy of chromosome 17 with TOP2A deletion. Similarly, a gain of all markers except TP53 was found in 14 cases.…”

Optimizing sparse sequencing of single cells for highly multiplex copy number profiling

“…5). Some occurred at genes with established clinical significance in breast cancer, such as the amplification of cyclin D1 (CCND1) (Arnold and Papanikolaou 2005) on Chromosome 11 and topoisomerase (DNA) II alpha (TOP2A) (Engstrom et al 2014) on Chromosome 17, while others occurred at genes for which experimental evidence exists for involvement in cancer, such as the homeobox protein SIX6 (Soulier et al 2005) on Chromosome 14 and PREX1 (Sosa et al 2010) on Chromosome 20. Together, these data provide strong evidence of the power of highly multiplex single-cell sequencing in resolving subclonal structure and illustrating genomic heterogeneity present within the genomes of human tumors.…”