The Danish Mole Project

Hydatidiform mole (HM) is an abnormal pregnancy, characterized by trophoblastic hyperplasia, vesicular swelling of the chorionic villi, and without a viable fetus.
After a molar pregnancy, there is a 10 % risk of gestational trophoblastic neoplasia (GTN)
The phenotype hydatidiform mole seems always to be caused by abnormalities involviong genes regulated by parental imprinting. Most hydatidiform moles are diploid or triploid, with a surplus of paternally inherited genes, however a number of other genetic variants have been observed.
In the Danish Mole Project We are collecting samples from hydatidiform moles and other trophoblastic diseases. These samples are used for basic and clinical research
1) Correlation between the macroscopic phenotype and the ploidy, and the clinical outcome
In a prospective study, all samples are classified according to the macroscopical phenotype, and ploidy is determined by karyotyping. The results are correlated with information on whether the patient subsequently needs cancer chemotherapy.
2) Diagnostics using analysis of circulating DNA and circulating cells in diagnostics of the origin of trophoblastic neoplasias. In this project we developing methods for diagnosing the origin of malignant trophoblastic tumours. With these methods we will analyse the prognostic value of parental origin of the genome in these tumours. Next we will attempt to further refine the methods, in order to improve the follow-up of patients after being treated for a trophoblastic disease.
Collaboration with Dept.s of Clinical Genetics, Gynaecology, and Oncology, AUH, and Arcedi Biotech ApS
3) Development of methods for determing ploidy without karyotyping
Often the trophoblastic disease is diagnosed after all tissue has been formalin fixed, making karyotyping impossible. We are developing methods for valid determining ploidy using Fluorescence In Situ Hybridiation and flow cytometry on formalin-fixed paraffin-embedded tissue
Collaboration with Inst. for Pathology, AAUH, Dept. of Pathology, AUH, and Dept. of Clinical Genetics, AUH.
4) Mapping imprinted genes relevant for early differentiation
By analyzing the parental origin of chromosomes showing aneuploidy and comparing with the phenotype in HMs, we are identifying genomic regions likely to habour/not harbour imprinted genes relevant for early differentiation. Further, HMs and HM-like conceptuses with diploid biparental genomes will be subjected to whole genome analysis of methylation.
Collaboration with BGI, China
5) Establishment of homozygous induced pluripotent stem cells (ipsc)
Most diploid androgenetic HMs are homozygous in every locus. By inducing stem cells from such cells and subsequently inducing re-differentiation, we can study the influence af individual genes early differentiation
Collaboration with colleagues at Dept. of Biomedicine, AU
6) The function of NLRP genes
Some women are genetically predisposed for achieving HMs, due to pathogenic variant in both copies of NLRP7. In mice and human oocytes we are studying the role of various NLRP genes in early differentiation.
Collaboration with colleagues at Dept of Biomedicine AU