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Single nucleotide polymorphisms of the EpCAM-coding gene TACSTD1 in patients with ovarian cancer and their potential translational aspects

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

EpCAM is overexpressed in many neoplasms including ovarian cancer. We screened the EpCAM-coding gene TACSTD1 for single nucleotide polymorphisms (SNPs), which could alter ovarian cancer risk, impact upon disease progression, or alter binding of the therapeutic EpCAM-binding antibody, catumaxomab.

Methods

DNA fragments of 10 healthy volunteers were analyzed to identify SNPs. Subsequently, DNA of ovarian cancer patients (n = 117) and age-matched healthy controls (n = 115) was genotyped by restriction fragment length polymorphism and pyrosequencing. TACSTD1 genotypes 4461T>C were cloned into a gene expression vector; Hek293 cells were subsequently used for stable transfection. FACS analysis of the transfected Hek293 cells was conducted with HO-3—the EpCAM binding site of catumaxomab—to determine antibody binding.

Results

One SNP was detected in exon 3 (4461T>C; rs1126497), resulting in an amino acid exchange at position 115 (Met115Thr). Another polymorphism was found in the 3′UTR (17225A>G; rs1421). Genotyping of patients and controls for these SNPs did not reveal significant differences in genotype distribution. Regarding 17225A>G, the homozygous AA-genotype was associated with diminished progression-free survival (PFS; p = 0.032). Overall survival, FIGO-stage, grading, and age did not differ significantly between genotypes. FACS analysis of transfected Hek293 cells overexpressing EpCAM 115Met/Thr showed binding of HO-3 to both proteins.

Conclusions

The AA-genotype of 17225A>G seems to be associated with diminished PFS in ovarian cancer patients. The amino acid exchange resulting from 4461T>C does not appear to alter binding of HO-3, suggesting that treatment with catumaxomab can be offered to patients regardless of their TACSTD1-genotype.

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Conflict of interest

This manuscript has been approved by all authors. There are no relationships that may present conflicts of interest.

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Authors and Affiliations

  1. Institute of Pharmacogenetics, Medical Faculty, University of Duisburg-Essen, Essen, Germany

    Martin Heubner & Winfried Siffert

  2. Department of Obstetrics and Gynaecology, Medical Faculty, Clinic of Obstetrics and Gynaecology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany

    Martin Heubner, Sabine Kasimir-Bauer & Rainer Kimmig

  3. Department of Obstetrics and Gynaecology, Medical Faculty, University Hospital Dresden, University of Dresden, Dresden, Germany

    Pauline Wimberger

  4. Institute of Anatomy, Medical Faculty, University of Duisburg-Essen, Essen, Germany

    Bernhard B. Singer

  5. TRION Research GmbH, Martinsried, Germany

    Peter Ruf

  6. DKTK Deutsches Konsortium für translationale Krebsforschung, Partnerstandorte Essen/Düsseldorf und, Dresden, Germany

    Martin Heubner, Pauline Wimberger, Sabine Kasimir-Bauer, Rainer Kimmig & Winfried Siffert

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  1. Martin Heubner
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  2. Pauline Wimberger
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  3. Sabine Kasimir-Bauer
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Corresponding author

Correspondence to Martin Heubner.

Additional information

Martin Heubner has been supported by the IFORES program of the University of Essen.

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Heubner, M., Wimberger, P., Kasimir-Bauer, S. et al. Single nucleotide polymorphisms of the EpCAM-coding gene TACSTD1 in patients with ovarian cancer and their potential translational aspects. Arch Gynecol Obstet 292, 1367–1372 (2015). https://doi.org/10.1007/s00404-015-3802-2

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  • DOI: https://doi.org/10.1007/s00404-015-3802-2

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