ATM and TP53 mutations show mutual exclusivity but distinct clinical impact in mantle cell lymphoma patients
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- ATM, Mantle cell lymphoma, SOX11, TP53, p21, survival,
- MeSH
- Ataxia Telangiectasia Mutated Proteins genetics metabolism MeSH
- Genetic Predisposition to Disease * MeSH
- Genetic Association Studies MeSH
- Humans MeSH
- Lymphoma, Mantle-Cell genetics mortality pathology therapy MeSH
- Mutation * MeSH
- Biomarkers, Tumor MeSH
- Tumor Suppressor Protein p53 genetics metabolism MeSH
- Prognosis MeSH
- Sequence Deletion MeSH
- SOXC Transcription Factors genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ATM protein, human MeSH Browser
- Ataxia Telangiectasia Mutated Proteins MeSH
- Biomarkers, Tumor MeSH
- Tumor Suppressor Protein p53 MeSH
- SOX11 protein, human MeSH Browser
- TP53 protein, human MeSH Browser
- SOXC Transcription Factors MeSH
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 ATM or TP53 defects plays an important role in MCL pathogenesis. Using deep next-generation sequencing we analyzed the mutual composition of ATM and TP53 mutations in 72 MCL patients, and assessed their impact on progression-free survival (PFS) and overall survival (OS). Mutated ATM and TP53 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 TP53 gene was associated with the significantly reduced PFS and OS and the same output was observed when ATM and TP53 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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