Targeted genomic investigations in a population-based cohort of mantle cell lymphoma reveal novel clinically relevant targets

Abstract

Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm that follows a heterogeneous clinical course. Recurrent mutations have been described, but their applicability in the clinical setting is currently limited. The main reasons are challenges in the sequencing of DNA retrieved from formalin-fixed tissue commonly used for tissue collection in clinical biobanks. In this study, we sequenced 77 samples from a population-based de novo MCL cohort to investigate the utility of targeted sequencing in guiding personalized treatment approaches. Tumors were genetically variable, and a similar genetic landscape as previous studies using non-formalin fixed samples was identified, with recurrent mutations including ATM, KMT2D, and TP53. Novel alterations that can be considered actionable and/or indicative of treatment response were also identified. Our approach shows the potential benefits of using target sequencing of formalin fixed samples to facilitate treatment selection and individualized clinical decisions in MCL.