Correlation of HER2, MDM2, c-MYC, c-MET, and TP53 Copy Number Alterations in Circulating Tumor Cells with Tissue in Gastric Cancer Patients: A Pilot Study

胃癌患者循环肿瘤细胞中 HER2、MDM2、c-MYC、c-MET 和 TP53 拷贝数变异与组织之间的相关性:一项初步研究

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作者:Fatemeh Nevisi, Marjan Yaghmaie, Hossein Pashaiefar, Kamran Alimoghaddam, Masoud Iravani, Gholamreza Javadi, Ardeshir Ghavamzadeh

Background

The analysis of the gene copy number alterations in tumor samples are increasingly used for diagnostic and prognostic purposes in patients with gastric cancer (GC). However, these procedures are not always applicable due to their invasive nature. In this study, we have analyzed the copy number alterations of five genes (HER2, MDM2, c-MYC, c-MET, and TP53) with a fixed relevance for GC in the circulating tumor cells (CTCs) of GC patients, and, accordingly, as a potential approach, evaluated their usage to complete primary tumor biopsy.

Conclusion

Our work suggests that the amplification of HER2 and c-MYC is in concordance with the CTCs and achieved biopsies, and, consequently, CTCs may act as a non-invasive alternative for recording the amplification of these genes among GC patients.

Methods

We analyzed the status of the copy number alterations of the selected genes in CTCs and matched biopsy tissues from 37 GC patients using fluorescence in situ hybridization.

Results

HER2 amplification was observed in 2 (5.41%) samples. HER2 gene status in CTCs showed a strong agreement with its status in 36 out of 37 patients’ matched tissue samples (correlation: 97.29%; Kappa: 0.65; p < 0.001). MDM2 amplification was found only in 1 (2.70%) sample; however, the amplification of this gene was not detectable in the CTCs isolated from this patient. c-MYC amplification was observed in 3 (8.11%) samples, and the status of its amplification in the CTCs indicated a complete agreement with its status in the matched tissue samples (correlation: 100%; Kappa: 1.0).

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