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    Aydin Raei Sadigh

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Interrogating the biomarker potential of methylated cell-free DNA in melanoma patients

Student name:

Aydin Raei Sadigh (PhD candidate)

Supervisors:

  1. Professor Elin Gray
  2. Dr Aaron Beasley

Summary of thesis:

The advent of immune checkpoint inhibitors (ICIs) has greatly improved the management of advanced melanoma. Given the varied response observed with immunotherapy, it is critical to identify biomarkers for monitoring treatment response and predicting potential patients who will benefit from ICIs. Circulating tumour DNA (ctDNA) has emerged as a promising “liquid biopsy” for melanoma. So far, ctDNA analysis has been primarily based on a patient’s mutational profile; however, mutation-driven ctDNA analysis remains suboptimal and given the ever-pressing issue of clonal evolution imposed by treatments, other types of molecular targets, such as cell-free DNA methylation, may be beneficial in improving sensitivity and specificity for ctDNA analysis.

In this project, firstly, pre-analytical variables affecting ctDNA methylation analysis will be evaluated. Secondly, through in-silico analysis, I will identify consensus melanoma-specific methylated sites that can be used as molecular target for ctDNA analysis to monitor and predict treatment response of patients. Finally, the predicted methylated sites will be evaluated in plasma from melanoma patients treated with ICIs to demonstrate clinical validity.

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