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ATM and TP53 mutations show mutual exclusivity but distinct clinical impact in mantle cell lymphoma patients. | LitMetric
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 or defects plays an important role in MCL pathogenesis. Using deep next-generation sequencing we analyzed the mutual composition of and mutations in 72 MCL patients, and assessed their impact on progression-free survival (PFS) and overall survival (OS). Mutated and 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 gene was associated with the significantly reduced PFS and OS and the same output was observed when and 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.
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