The Effects of Chemotherapy on TMN Progression

Patients with a known chemotherapy signature had a high prevalence of copy number alterations and TP53 mutations compared to TMN cases without chemotherapy signatures. All TMN's exposed to prior platinum-based therapy harbored a characteristic platinum mutational signature, consistent with a model in which one cell survived platinum-based DNA damage and expanded to clonal dominance. Conversely, only 41% of TMN exposed to prior melphalan-based Therapy harbored the characteristic melphalan mutational signature.