Lone Sunde

Research

The Danish Mole Project: Hydatidiform mole (HM) is an abnormal human conceptus, characterised by vesicular swelling of the chorionic villi and absent (complete mole, CHM) or abnormal (partial mole, PHM) embryonic differentiation. If a fetus is present, it is malformed and never viable. Most CHMs are diploid androgenetic (both chromosome sets derive from the father). Most PHMs are triploid, two chromosome sets originating from the father. Tetraploid, aneuploid, and diploid HMs with biparental genomes are rare.App. 1/1000 human pregnancies are HMs. App. 10% of HMs are followed by persistent trophoblastic disease (PTD). PTD can be cured by cancer chemotherapy.The Danish Mole Project started in 1986. The project is conducted as a collaboration between Institute of Biomedicine, Department of Clinical Genetics, and departments of gynaecology, pathology, and oncology in Jutland. Fresh frozen samples from app. 400 HMs and their mothers are stored. The collection of samples is ongoing.

Research interests

Our research both focuses on basic and clinical issues in relation to genetics in fertility and cancer:

We have observed that some HMs are mosaics, in that they both harbour cells that are diploid androgenetic and cells with diploid biparental genome. We are currently exploring the mechanism behind this mosaicism

How does a conceptus without maternal chromosomes arise? It is likely that a triploid HM arise by fertilization of an oocyte by two spermatozoas. However, it is unknown how conceptuses without maternal chromosomes, arise. We are currently testing the hypothesis that these arise from conceptuses with three pronuclei, via abnormal early cell divisions.

Which genes are subject to parental imprinting? As an embryo/a fetus is never present in a diploid androgenetic HM, at least one maternally imprinted gene seems necessary for early embryonic differentiation.  We hunt this gene by analysing the rare aneuploid HMs.

Mutations in NLRP7 or C6orf221 in the mother predispose to the molar phenotype in her conceptuses, although these may have a normal diploid biparental genome. We are exploring the role of the NLRP genes in relation to fertilisation, early development and cancer

HM -> PTD: We have shown that the risk of PTD after a triploid mole is very low, whereas the risk after a diploid mole is app. 20%. We now seek to refine these values: Is the risk after triploid mole identical to the risk after a non-molar conception? Can we predict which of the diploid moles that will progress to PTD?
PTD is traditionally regarded as a neoplastic disease; the cells grow invasively, the condition is fatal if left untreated, and PTD can be cured with cancer chemotherapy. However, the “malignant” cells are not derived from the patient (the mother) but from the HM (the conceptus). We look for genetic similarities/differences between PTD and cancer.

We study these issues, by analysing the genetics and epigenetics of HMs, other similar conceptuses and their parents and by correlating the results with the morphology of the conceptus and the outcome.

Methodologies

  • Karyotyping                     
  • Estimation of ploidy by flow cytometry 
  • DNA marker analysis, sequencing, arrayCGH

Collaborators and centres

Collaborators:

  • Prof. Rosemary Fisher, Institute of Reproductive and Developmental Biology, Imperial College, London, UK
  • Prof. Rima Slim, Montreal General Hospital Research Institute, Canada
  • Prof. Urvashi Surti, Magee-Women’s Research Institute, University of Pittsburgh, Pennsylvania, USA
  • Prof. Per Guldberg, Institute of Cancer Biology, Copenhagen
  • MD, PhD Isa Niemann, Center for Trofoblastic Diseases, Prof. Jan Blaakær, Prof. Jakob Ingerslev, PhD Johnny Hindkjær, PhD Birte Degn, Prof. Ole Bjarne Christiansen, Depts. of Gyn. and Obst., Aarhus University Hospital
  • MD Astrid Petersen, MD Anni Grove, MD Helle Lund, and MD Estrid Stæhr Hansen, Depts. of Pathology, Aarhus University Hospital
  • MD, PhD Niels Katballe, Dept. of Thoracic Surgery, Aarhus University Hospital
  • Ass. prof.,PhD, MPH, Ellen Mikkelsen, and ass. prof., MD, PhD, Mette Nørgaard, Dept. of Clin. Epidemiol., Aarhus University Hospital
  • Prof. Lars Bolund, BGI/ HuaDa-Shenzhen, Shenzhen, China, and Inst. f. Biomedicine, AU
  • Ass. prof., MD, PhD Uffe Birk Jensen and ass. prof. PhD, Mette Nyegaard, Inst. f. Biomedicine, AU

Centres:
Genetics in Reproduction and Development, Dept. of Biomedicine, Health, AU. Ass. prof. Karin Lykke-Hartmann

Research group members

Typically, the group supervises 2-3 research year students, 2-3 PhD-students and junior doctors performing other research projects.  

Group leader

Lone Sunde

M
H bygn. 1242, 131
P +4587167765
P +4540144364

Publications

Sortér efter: Dato | Forfatter | Titel

Henvendelse om denne sides indhold: 
Revideret 20.09.2017