Splice Variants And Non-Coding RNA Expression In Breast Cancer Patients With A Certain Type Of Mutant TP53

The proposed project aims to identify biological pathways specifically perturbated in patients with a certain type of mutant TP53 at both array and deep sequencing mRNA expression level: 1. Splice Variants and non-coding RNA expression in breast cancer: Using next generation RNA sequencing of 55 samples from Radium Hospital and CINJ, we have identified splice variants, large non-coding RNA and alternative usage of promoters which are differentially expressed in clinical and histo-pathological subtypes of breast cancer. Currently, we are validating the existence of these gene and protein variants, both here in Norway and in our collaborator at Rutgers. In addition, one of my PhD students, Sunniva Bjørklund is at present in Rutgers to perform functional s tudies of the alternative transcripts. She will also sequence p53 mutations in the tumors from USA (the tumors from Radium Hospital are already profiled). This will allow us to identify the role of the p53 pathway in the observed anomalies, which will be analysed with the group of our collaborator Dr. Levine at the Institute for Advanced Study in Princeton, who is a world leading expert in the TP53 field. 2. Identifying the pathways affected by p53 mutations in breast cancer: In a second study, we will analyze a rich dataset consisting of microarray gene expression, p53 mutation status, clinical and long term follow up (survival data) for a large cohort of breast cancer samples from Norway. The goal of this study is to gain insight into the predominant tumor driver pathways that have a differential impact on prognosis, survival and treatment response. Any signal identified will be followed up with laboratory validation studies, both here in Oslo as well as at CINJ. Another PhD student of mine (Himanshu Joshi) has already visited Rutgers earlier this year and will be returning to Rutgers for three months this Fall to complete a bioinformatics on the pathway identification analysis.