Malignant lymphomas are the fourth most frequent cancer in men and women and affects patients of all ages. Lymphomas are very diverse in their biology and clinical behaviour and unfortunately, the current standard of care fails to eliminate the lymphoma in a substantial proportion of patients who are then very likely to succumb to their disease. The causes for these unfavorable clinical outcomes are partly due to the lack of novel therapeutic targets. This study aims to significantly improve the survival for patients with a specific type of lymphoma, called primary mediastinal large B cell lymphoma (PMBCL). We have discovered novel mutations of the IL4R gene in a subset of PMBCL patients that activates oncogenic signaling ("JAK-STAT signaling") and likely plays an important role for the formation of these cancers. Our findings may provide a rational therapeutic target for future treatments; maximizing cure rates and minimizing treatment-related side effects.