Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2017

Erindi/veggspjald / Talk/poster E28

Potential Role of an Autophagy Gene in Breast Tumor Development

Höfundar / Authors: Arsalan Amirfallah(1,5), Eydís Þ. Guðmundsdóttir(1), Adalgeir Arason(2), Bjarni A. Agnarsson(3,5), Óskar Þór Jóhannsson(4), Rósa Björk Barkardóttir(2,5) and Inga Reynisdóttir(1,5)

Starfsvettvangur / Affiliations: 1.Cell Biology Unit and 2.Molecular Pathology Unit at 3. Pathology Dept, 4. Dept of Oncology, Landspitali – The National University Hospital of Iceland; 5. BMC, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

Kynnir / Presenter: Arsalan Amirfallah

Introduction: Breast cancer is the most common cancer in women worldwide. Many kinds of rearrangements in the genome can lead to defects/dysregulation of genes that support tumor formation. The objective of this study was to identify a gene with a role in breast cancer by analyzing gene fusions.
Methods: Gene fusions from breast cancer cell lines and breast tumors were compared. They were obtained from RNA-Seq data from GEO at NCBI, analyzed using the SOAPfuse algorithm, purchased from MediSapiens, and gathered from published papers, the majority of tumors were from The Cancer Genome Atlas (TCGA). Gene fusions in common between tumors and cell lines were confirmed through RT-PCR, Sanger sequencing, and the individual gene partners analyzed by correlating the quantity of DNA and mRNA available in a Nordic breast cancer databank (BASE2) and TCGA. The gene with the best correlation was confirmed by measuring DNA and mRNA with qPCR in breast tumors (n = 144) and the quantities correlated with clinical and pathological data.
Results: The top ranking gene has a role in autophagy and preliminary data show a positive correlation between the gene´s mRNA and DNA levels in a HER2 Enriched subtype (r = 0.79, p < 0.001). Furthermore, its mRNA expression was higher among tumors with high grade (p=0.007), HER2+ (p=0.0006), and metastasis (p=0.04). Patients with high levels of DNA and mRNA had shorter overall survival (p= 0.01, p= 0.03).
Conclusions: The data suggest that analyzing genes involved in fusions may be a successful mean to identify genes with a role in breast cancer. The results have to be verified in another Icelandic cohort as well as in the TCGA data. If confirmed, analysis will be performed to understand how this autophagy gene influences the development of breast cancer.