Inherited Clues: How Our Genes Influence Post-Treatment Blood Cancer

This project involves targeted genomic sequencing of hundreds myeloid neoplasm (MN) samples to explore the landscape of germline mutations contributing to disease development and progression.

A primary focus is to differentiate the germline mutational profiles between therapy-related MN (t-MN) and de novo MN, aiming to uncover distinct patterns that may inform diagnosis and risk stratification. 

The study also seeks to investigate how specific germline mutations influence somatic clonal evolution and shape the disease phenotype over time.

Through this comprehensive genomic approach, we aim to discover novel germline mutations associated with t-MN pathogenesis.

In parallel, the project will examine the clinical relevance of these germline mutations, particularly in relation to treatment outcomes. By correlating genetic findings with clinical data, we aim to identify germline variants that may serve as predictors of treatment response or toxicity. This could ultimately inform personalised therapeutic strategies and risk mitigation approaches.

To complement the genomic and clinical analyses, in vitro functional studies will be conducted to assess the biological impact of select germline mutations. These experiments will specifically evaluate mutations hypothesised to contribute to treatment-related toxicities, providing mechanistic insights and potential biomarkers for guiding clinical decision-making.

This project is funded by the Medical Research Future Fund and Cancer Australia