The Somatic Mutational Landscape Of Blm-Deficient Tumors: Finding Clues for Future Therapeutic Opportunities

Awardee: Richarda de Voer

Institution: Radboud University Medical Center (Stichting Radboud Fonds)

Awarded: $150,000

Funding Period: April 1, 2025 – March 31, 2027

Summary: Despite cancer surveillance strategies >80% of individuals with Bloom syndrome (BSyn) will have developed a malignancy by the age of 40 years. Treatment of malignancies in individuals with BS is still mostly based on standard-of-care treatments. With this proposal we aim to unravel the (mutational) mechanisms responsible for tumor initiation and progression in individuals with BSyn. We expect to gain insights into the processes relevant for tumor development in individuals with BSyn, leading to clues for future therapeutic opportunities. We will repurpose archived tumors from individuals with BSyn to:

1. Perform whole-exome or whole-genome sequencing to determine the somatic single base and small indel mutation landscape, investigate mutational signatures of defective DNA repair, mutated driver genes and identify potential signs of homologous recombination deficiency (HRD);

2. Explore the immune landscape of tumors using multiplex immunohistochemistry.