Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin lymphoma (NHL). In recent years, a deeper understanding of the genetic subtypes of diffuse large B lymphoma has been reached, and these advances have also been applied to research on relapsed and refractory diffuse large B-cell lymphoma (RRDLBCL). We screened 1495 documents, compiled the whole-exome sequencing data of several studies, formed a data set including 92 observations, and performed association analysis on the high-frequency mutations among them. The most common mutations in the data set include TTN (34/92, 37.0%), KMT2D (29/92, 31.5%), TP53 (25/92, 27.2%), IGLL5 (25/92, 27.2%), CREBBP (21 /92, 22.8%), BCL2 (21/92, 22.8%), MYD88 (20/92, 21.7%), and SOCS1 (19/92, 20.7%). Among these, CREBBP, KMT2D, and BCL2 have a strong association with each other, and SOCS1 has a strong association with genes such as ACTB, CIITA, and GNA13. There is also a strong association between SOCS1 and STAT6. Though TP53 and MYD88 lack significant associations with most genes, the association between MYD88 and PIM1 is significant. Through SOM clustering and expression-level analysis of common gene mutations, we believe that RRDLBCL can be divided into four main types: (1) JAK-STAT-related type, including STAT6, SOCS1, ITPKB, CIITA, and B2M. The expression lineage is similar to PMBL and cHL. (2) EZB type: BCL2 and EZHZ are the main types of mutations. Epigenetic mutations such as KMT2D and CREBBP are more common in this type, and are often accompanied by BCL2 mutations. (3) MCD type, including MYD88, CD79B and PIM1. These genes are involved in the BCR signaling pathway and related pathways, and are connected by the common NF-κB pathway. (4) Undefined type (Sparse Mutation type). These patients are mainly individuals with sparse mutations, including some patients with TP53 mutations (30.3%, 10/33), but who generally lack characteristic mutations. Among the common gene mutations, the expression changes in BCL2, PIM1, STAT6, ITPKB, and GNA13 have more significant prognostic significance. We also reviewed the literature from recent years concerning the previously mentioned common gene mutations.
Primary diffuse large B cell lymphoma of the common bile duct causing obstructive jaundice