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May 2, 20265 citations

Integrative Molecular Analysis Reveals Determinants of Clinical Outcomes in TP53-Mutated Diffuse Large B-Cell Lymphoma.

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MUManik UppalBBBhavneet BhinderAMAndrew R. Marderstein

Key Points

  • This research aims to identify molecular determinants affecting clinical outcomes in TP53-mutated diffuse large B-cell lymphoma (DLBCL).
  • Analyzed clinical and molecular data from 3,091 patients with newly diagnosed DLBCL.
  • Utilized frontline rituximab-based immunochemotherapy regimens.
  • Performed targeted or whole-exome sequencing and bulk RNA sequencing for data analysis.
  • High variant allele frequency (VAF) negatively impacts progression-free survival.
  • The study found that intrinsic features and co-occurring genomic lesions influence outcomes.

Abstract

PURPOSE: -mutant DLBCL. METHODS: Clinical and molecular data for 3,091 patients were derived from 10 cohorts of patients with newly diagnosed DLBCL treated with frontline rituximab-based immunochemotherapy regimens. Targeted or whole-exome/whole-genome sequencing was available for all patients. Bulk RNA-seq was analyzed for 591 patient samples. The primary outcome measures were progression-free survival (PFS) and overall survival (OS). RESULTS: -mutant DLBCL and abrogated the deleterious impact of high VAF, irrespective of patients' age. CONCLUSION: -mutant DLBCL is dependent on intrinsic features, such as VAF, and modulated by co-occurring genomic lesions or lymphoma cell-intrinsic or microenvironmental expression patterns.

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Cite This Study

Uppal et al. (2026) studied this question.

synapsesocial.com/papers/69f5951171405d493a0000bdhttps://doi.org/10.1200/jco-25-01928
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