The OncoMark Process

The OncoMasTR Technology was originally developed by researchers in Trinity College Dublin (TCD) in collaboration with Prof. William Gallagher of University College Dublin (UCD) (who was also founder and the Chief Scientific Officer of OncoMark). The central hypothesis of the work was to identify upstream ‘drivers’ of cancer progression, rather than ‘passenger’ genes, which other cancer biomarker signatures had identified. Upstream drivers represent a more accurate and reliable indicator of tumour progression.

Background

Several multigene prognostic signatures, which identify the risk of women with early stage, lymph node-negative breast cancer of developing a recurrence after surgical resection, have been developed in recent years [1],[2]. Many of these have been adopted in the clinic and have proven useful in terms of stratifying patients into lower and higher recurrence risk groups. However, since there was little overlap in the genes represented in these signatures, it was hypothesized that identifying and measuring gene expression of the upstream Master Transcriptional Regulators (MTRs) would allow the development of more accurate tests to help inform on best treatment options.

Approach

A novel bioinformatic algorithm termed ARACNe [3],[4]  was used to predict the upstream MTRs of two independent breast cancer prognosis biomarker signatures. ARACNe uses networks constructed from gene expression datasets to infer direct transcriptional interactions. A panel of Master Transcriptional Regulators (MTRs), commonly associated with poor prognosis in existing tests and that shared a common role in cell proliferation, was identified.

In this way, a mechanistically anchored panel of biomarkers was identified comprising up to 10 MTRs. These were brought forward for the development of the OncoMasTR Test.