Patterns of somatic genetic alteration reveal the life history of a cell | Dr Aidan Flynn

DR AIDAN FLYNN
Postdoctoral Scientist, Rare Disease Oncogenomics
UMCCR & Department of Clinical Pathology

Differentiation of normal cells is dictated by heritable cellular programs controlled by epigenetic mechanisms. It has been known for some time that these normal cellular programs can be retained during tumorigenesis and reflected by global gene-expression and DNA methylation profiling. More recently there is a growing appreciation for use of DNA mutation data as an orthogonal method for cancer type classification. Firstly, gene mutations can be pathognomonic and restricted to certain cancer types. Secondly, next-generation sequencing enables genome-wide analysis of the patterns of somatic mutation, giving rise to what has been termed “mutation signature analysis”.

Mutational signatures involving a 96-trinucleotide pattern represent a wide array of endogenous and exogenous mutational processes, some which have diagnostic and therapeutic relevance. Finally, recent studies have demonstrated the complex interplay of DNA structure and mutational processes defining the distribution of somatic mutations across the genome. So called “positional mutational profiling” can be used to classify cancer cell of origin.

Aidan will present collaborative work done with the Hartwig Medical Foundation using a tool called CUPPA that combines analysis of oncogenic drivers, mutational signatures and positional mutation profiling for diagnosis of cell of origin in diagnostically challenging cancers and also to resolve the cell of origin of a rare skin cancer.

Dr Aidan Flynn began his research career as a Research Assistant at the Peter MacCallum Cancer Centre in 2006. In 2015, he completed his PhD under the supervision of Dr Richard Tothill and Professor Rodney Hicks.  During his PhD, Aidan performed genomic profiling of a large cohort of Pheochromocytomas and Paragangliomas (PPGL), leading to the to the publication of the first survey of the genomic landscape of PPGL.  After completing his PhD, Aidan moved to Denmark to pursue a post doctoral placement at the university of Copenhagen.  Aidan’s post doctoral research focussed on the mechanisms of clonal evolution in glioblastoma and how they contribute to treatment escape and relapse.  Aidan has recently returned to Melbourne to continue his work with Professor Hicks and Dr Tothill on the genomics of neuroendocrine tumours and cancers of unknown primary.