Cancer Core Europe (CCE) Lecture - Dissecting the function of copy number alterations in cancer

Welcome to the next lecture, hosted by Vall Hebron Institute of Oncology (VHIO): Speaker: Francisco Barriga, Group Leader, VHIO, Barcelona Spain Thursday, April 10 ‒ Time 15:00 - 16. 00 CET Join Zoom Meeting us06web.zoom.us/j/88644457350 Meeting ID: 886 4445 7350 Abstract Chromosomal deletions are prevalent in cancer, yet their function remains ill-defined. One of the most frequent losses affects chromosome 9p21.3, which disables the CDKN2A/B tumor suppressor genes. Intriguingly, half of 9p21.3 deletions encompass a cluster of 16 type I interferons (IFNs) whose co-deletions have not been functionally characterized. To dissect this biology we developed MACHETE (Molecular Alteration of Chromosomes with Engineered Tandem Elements), a genome engineering strategy to create megabase-sized deletions. 9p21.3-syntenic deletions in a mouse model of pancreatic cancer revealed that concomitant loss of Cdkn2a/b and IFNs led to immune evasion and metastasis. Mechanistically, IFN co-deletion disrupted antigen-presenting cells and facilitated escape from CD8+ T cell surveillance in a cell extrinsic manner. Our results establish co-deletions of the IFN cluster as a pervasive route to tumor immune evasion and metastasis. This study establishes a framework to dissect the functions of genomic deletions in cancer and beyond. What is Cancer Core Europe (CCE)? Cancer Core Europe is a consortium of seven leading cancer centres (www.cancercoreeurope.eu). CCEs members are driven by a strong will to reshape the cancer research model to ultimately increase the European Union’s competitiveness as a place to conduct cutting-edge research that’s translated to the clinic to deliver more personalized medicine. What is the content and aim of the CCE Lecture? The CCE Lecture serie is a CCE-internal event, which educates and informs about state of the art research within the seven centers and is aimed to increase awareness among partners about each other’s activities and potential for collaboration.