DR-516 Genetic, epigenetic and transcriptomic determinants of heterogeneity-driven variation in radiation response in oesophageal adenocarcinoma

Oesophagogastric adenocarcinoma (OGA) is associated with substantial heterogeneity. Less than 1 in 5 patients respond adequately to external beam radiotherapy (EBRT). Using a patient-derived organoid (PDO) biobank, we have demonstrated that a back-up DNA damage response pathway, alternative end joining (A-EJ), contributes to resistance to high radiation doses and have defined a multi-gene transcriptomic signature that associates with radiation response. Using Hartwig whole genome/RNA sequencing data, we will explore whether A-EJ and signature genes are enriched in radiation-treated OAC samples. This will provide supporting evidence to improve outcomes in OAC by guiding personalised approaches and the introduction of novel radiosensitisers.

Rebecca Fitzgerald, Early Cancer Institute, University of Cambridge, United Kingdom