Characterizing the Mutational Landscape of Diffuse Large B-Cell Lymphoma in a Prospective Cohort of Mexican Patients

Int J Mol Sci. 2024 Aug 28;25(17):9328. doi: 10.3390/ijms25179328.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy worldwide. Molecular classifications have tried to improve cure rates. We prospectively examined and correlated the mutational landscape with the clinical features and outcomes of 185 Mexican patients (median age 59.3 years, 50% women) with newly diagnosed DLBCL. A customized panel of 79 genes was designed, based on previous international series. Most patients had ECOG performance status (PS) < 2 (69.2%), advanced-stage disease (72.4%), germinal-center phenotype (68.1%), and double-hit lymphomas (14.1%). One hundred and ten (59.5%) patients had at least one gene with driver mutations. The most common mutated genes were as follows: TP53, EZH2, CREBBP, NOTCH1, and KMT2D. The median follow-up was 42 months, and the 5-year relapse-free survival (RFS) and overall survival (OS) rates were 70% and 72%, respectively. In the multivariate analysis, both age > 50 years and ECOG PS > 2 were significantly associated with a worse OS. Our investigation did not reveal any discernible correlation between the presence of a specific mutation and survival. In conclusion, using a customized panel, we characterized the mutational landscape of a large cohort of Mexican DLBCL patients. These results need to be confirmed in further studies.

Keywords: Latin America; diffuse large B-cell lymphoma; genomics; mutational landscape; prognostic.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • CREB-Binding Protein / genetics
  • DNA-Binding Proteins
  • Enhancer of Zeste Homolog 2 Protein* / genetics
  • Female
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Lymphoma, Large B-Cell, Diffuse* / mortality
  • Male
  • Mexico / epidemiology
  • Middle Aged
  • Mutation*
  • Neoplasm Proteins / genetics
  • Prognosis
  • Prospective Studies
  • Receptor, Notch1 / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Young Adult

Substances

  • Enhancer of Zeste Homolog 2 Protein
  • EZH2 protein, human
  • Receptor, Notch1
  • KMT2D protein, human
  • CREB-Binding Protein
  • CREBBP protein, human
  • Tumor Suppressor Protein p53
  • NOTCH1 protein, human
  • TP53 protein, human
  • Neoplasm Proteins
  • DNA-Binding Proteins

Grants and funding

This research received no external funding.