ATM and TP53 mutations show mutual exclusivity but distinct clinical impact in mantle cell lymphoma patients

Abstract

Mantle cell lymphoma (MCL) is characterized by the hallmark t(11;14)(q13;q32) translocation, leading to cyclin D1 over-expression. Additionally, disrupting the DNA damage response pathway through <i>ATM</i> or <i>TP53</i> defects plays an important role in MCL pathogenesis. Using deep next-generation sequencing we analyzed the mutual composition of <i>ATM</i> and <i>TP53</i> mutations in 72 MCL patients, and assessed their impact on progression-free survival (PFS) and overall survival (OS). Mutated <i>ATM</i> and <i>TP53</i> alleles were found in 51% (37/72) and 22% (16/72) of the cases examined, respectively, with only three patients harboring mutations in both genes. Only a mutated <i>TP53</i> gene was associated with the significantly reduced PFS and OS and the same output was observed when <i>ATM</i> and <i>TP53</i> defective groups included also sole deletions 11q and 17p, respectively. Determining the exact ATM/p53 pathway dysfunction may influence the selection of MCL patients for innovative therapies based on the targeted inhibition of selected proteins.