Master's project

Emma Roger Andersen, BSc

The translocation of the ALK (anaplastic lymphoma kinase) gene is one of the prevalent oncogenic drivers in non-small-cell lung cancer (NSCLC), which is a serious disease with a high incidence and mortality rate. Tissue samples from cancer patients are used for diagnosis to reveal ALK fusions, but the procedure is invasive. As the tumor cells shed their ctDNA into the peripheral bloodstream, it enables a unique possibility to sample and monitor cancer by analyzing ctDNA in the plasma using polymerase chain reaction (PCR) and Next Generation Sequencing (NGS). The procedure is less invasive, however, NGS struggle to identify these rearrangements and differentiate between the variants.

Chromosomal inversion between ALK and Echinoderm microtubule-associated protein-like 4 (EML4) at chromosome 2 leads to the formation of ALK-EML4 fusion. To improve the sensitivity of the EML4-ALK detection using NGS, we developed an algorithm (DNAfusion) to detect the fusions during my bachelor project in the spring of 2022 and these results are now published (reference). We achieved great results but aimed to update the algorithm to give more informative results. Since the fusion can be divided into different fusion variants and these can affect the treatment, we improved the algorithm to distinguish between the variants for my research project in the spring of 2023.

For my master’s thesis, I aim to analyze the impact of different EML4-ALK variant types and the presence of co-mutations for treatment response. I will examine these and determine if there are any differences in the ctDNA clearance among patients and their variants. I aim to draw a possible connection between the variants and their clinical significance including response to treatment.

I hope my research can improve treatment strategies and thereby survival.