Poster Presentation 16th Asian Conference on Transcription 2019

Good genes gone bad: are placental genes hijacked by cancer cells to facilitate invasion? (1182)

Chi Lynch-Sutherland 1 , P A Stockwell 1 , M R Eccles 1 2 , A Chatterjee 1 2 , E C Macaulay 1
  1. Department of Pathology, University of Otago, Dunedin School of Medicine, Dunedin, NZ
  2. Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, NZ

The human placenta may offer novel insights into the molecular mechanisms that drive cancer invasion and metastasis. During early pregnancy the placenta invades into the uterus and manipulates the maternal immune response, showing striking similarities to cancer. The placenta and cancer lack DNA methylation at some retrotransposon sequences. Demethylation of retrotransposons in the placenta has given rise to new genes and regulatory elements, some of which are critical for placental development. Surprisingly, these placental genes are also overexpressed in a number of cancers, but their function is not yet known. This project seeks to document the abundance and diversity of functional retrotransposons in the placenta and reveal the functional role of these elements in cancer. We have developed a bioinformatic pipeline to identify functional retrotransposons in the placenta and other early developmental stages. Expression of these elements has also been investigated in melanoma revealing that they are upregulated in comparison to corresponding somatic tissue. Currently we are investigating the mechanism which permits activation of these functional retrotransposons in cancer along with the functional significance. We expect that reactivation of these genes and regulatory elements occurs as a consequence of dedifferentiation associated epigenetic changes and may drive further differentiation of tumours. Moreover, there is compelling evidence that dedifferentiation can contribute to invasion and metastasis. The specificity of these elements to the placenta and cancers means they could to provide valuable diagnostic and therapeutic targets, and may help to identify cancers at a higher risk of metastasis.