Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2019
Erindi/veggspjald / Talk/poster E39
Höfundar / Authors: Arsalan Amirfallah1,5, Adalgeir Arason2,5, Oskar Þor Johannsson4, Bjarni A. Agnarsson3,6, Rosa Bjork Barkardottir2,5, Inga Reynisdottir1,5
Starfsvettvangur / Affiliations: 1. Cell Biology Unit at the Pathology Dept., Landspitali – The National University Hospital of Iceland, 101Reykjavík, Iceland. 2. Molecular Pathology Unit at the Pathology Dept., Landspitali – The National University Hospital of Iceland, 101 Reykjavik, Iceland. 3. Pathology Dept, Landspitali – The National University Hospital of Iceland, 101 Reykjavik, Iceland. 4. Dept. of Oncology, Landspitali – The National University Hospital of Iceland, 101 Reykjavik, Iceland. 5. Biomedical Center, Laeknagardur, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland. 6. Faculty of Medicine, University of Iceland, Saemundargata 2, 101 Reykjavik, Iceland
Kynnir / Presenter: Arsalan Amirfallah
Breast cancer is the most common cancer in women worldwide. Fusion genes result from genomic structural changes can result in changes in gene expression that affect tumour development. The objective of this study was to identify a gene with a role in breast cancer by analyzing gene fusions.
Fusion genes, identified through bioinformatics pipelines in breast cancer cell lines and tumors, were compared. The fusion genes in common were confirmed by qRT-PCR and sequencing, and then filtering criteria were applied. The DNA and mRNA quantity of the chosen individual genes, available from public databanks, were correlated to nominate candidates. The expression of the top ranked gene was measured by qRT-PCR in two Icelandic breast cancer cohorts, an exploratory cohort (n = 141) and a validation cohort (n =277), and subsequently correlated with clinicopathological characteristics and survival. The results were followed-up in breast cancer cohorts from The Cancer Genome Atlas (n = 818) and METABRIC (n = 2509).
The mRNA levels of the top ranked gene Vacuole Membrane Protein 1 (VMP1) were significantly higher in breast tumor tissue than normal tissue, and its expression was significantly higher in HER2 positive tumours than HER2 negative tumours in all four cohorts analyzed.
High expression of VMP1 associated with breast cancer specific survival (BCSS) in cohort 1 (hazard ratio (HR) = 2.31, CI 1.27–4.18) and METABRIC (HR = 1.26, CI 1.02–1.57) and also after adjusting for HER2 expression in cohort 1 (HR = 2.03, CI 1.10–3.72). The results suggest that an increase in mRNA levels of VMP1 is a potential marker of poor prognosis in breast cancer, particularly in HER2 positive cases. Further studies are needed to elucidate how VMP1 could affect pathways supportive of tumorigenesis.