FBI-1 amplification in gestational trophoblastic disease

Abstract

Gestational Trophoblastic Disease (GTD) encompasses a spectrum of disease that involves abnormal trophoblastic proliferation. It includes hydatidiform mole (HM), placental site trophoblastic tumor (PSTT), epithelioid trophoblastic tumor (ETT) and choriocarcinoma (CCA). While HMs are abnormal pregnancies with limited invasive potential, CCAs are true malignancies requiring chemotherapy. Although the majority of HM is resolved by surgical intervention, approximately 8-30% of them would develop into persistent GTD. In addition to that, being the most aggressive neoplasm in GTD, choriocarcinoma is a frankly malignant gestational trophoblastic neoplasm (GTN) that could be arisen from HM and could be fetal when widespread metastasis is developed. However, the underlying mechanisms of this disease progression are still unclear.

FBI-1 (Factor that Binds to Inducer of Short Transcripts (IST) protein 1) is a transcription factor that has been observed to be overexpressed in various types of human cancers. Recently, overexpression of FBI-1 is also reported in GTD and also in association with GTN development. However, the causes of FBI-1 overexpression in GTD are still unclear. This study aims to investigate gene amplification as a possible cause of FBI-1 overexpression in GTD. A quantitative real time PCR (qPCR) assay was established and was used to investigate ZBTB7A (the gene encoding FBI-1) amplification in GTD cell lines and clinical samples.

Using our qPCR assay, we demonstrated that ZBTB7A is not amplified in the CCA cell lines JEG-3 and JAR, in comparison with an immortalized trophoblast cell line HTR-8/SVneo. Testing ZBTB7A amplification in clinical samples also obtained similar findings although overexpression of FBI-1 was demonstrated in our previous studies. This is the first report illustrating absence of ZBTB7A amplification in cells with FBI-1 overexpression. There are other techniques that can detect gene amplification and/or other genetic and epigenetic mechanisms that may govern FBI-1 expression in GTD. Further studies will be worthwhile to pursue as FBI-1 is a potential target for cancer therapy.