Researchers from France identified 3 genetic subgroups of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Moreover, they found that the GNA13 mutant was associated with a higher risk of death and a shorter overall survival. 

According to the researchers, this knowledge “could help advance precision molecular medicine programs” for patients with DLBCL by targeting potential new biological pathways. 

Read more about the genetics of DLBCL

The study is published in the American Journal of Hematology.

Even though DLBCL patients are known to belong to distinct genetic subgroups, these subgroups are not determined at the time of relapse or refractory disease.

Here, the team led by Vincent Ribrag, MD, from Université Paris-Saclay, Gustave Roussy in Villejuif, France, conducted targeted next-generation sequencing analyses of tumor samples and fresh tissue obtained from patients with relapsed or refractory DLBCL to identify genetic subgroups and prognostic biomarkers at the time of relapse or refractory disease.

They found that the genes that were most frequently mutated were TP53, CREBBP, BCL2, KMT2D, and PIM1. Then using unsupervised clustering, they identified 3 genetic subgroups of patients. They called these the BST, TKS, and PCM groups, which were enriched in BCL2, SOCS1, and TNFRSF14 mutations, TP53, KMT2D, and STAT6 mutations, and PIM1, CD79B, and MYD88 mutations, respectively. 

The median overall survival for all patients was 11 months and even though there was no significant difference in overall survival between the 3 genetic subgroups the GNA13 mutant was associated with reduced overall survival and higher risk of death.

DLBCL is a type of non-Hodgkin lymphoma characterized by the formation of abnormally large B-cells that originate in the lymphatic system. It is an aggressive type of cancer that grows and spreads rapidly. Although the disease is not inherited a family history of lymphoma is a risk factor for the development of DLBCL.

Reference

Michot JM, Quivoron C, Sarkozy C, et al. Sequence analyses of relapsed or refractory diffuse large B-cell lymphomas unravel three genetic subgroups of patients and the GNA13 mutant as poor prognostic biomarker, results of LNH-EP1 study. Am J Hematol. Published online January 6, 2023. doi:10.1002/ajh.26835