Table 1.
Clinicobiological features of the 11 EBV+ DLBCL patients analyzed by whole-exome sequencing (WES).
Table 2.
Patient characteristics at diagnosis of EBV+ DLBCL (11 cases).
Fig 1.
Mutation spectrum of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma shown by whole-exome sequencing.
Frequency of substitutions in each sample for the six possible classes of mutation. The most common substitution was the transition C>T/G>A, followed by T>C/A>G.
Fig 2.
Distribution of mutations in different genome regions of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma detected by whole-exome sequencing.
(A) The percentages of mutations in different regions of EBV+ DLBCL cases. The percentage of mutations in exonic regions ranged from 3.49%–22.68% among these 11 cases. (B) We identified 3326 protein-coding genes with somatic mutations affecting exonic regions, with a range from 200 to 410 per case.
Table 3.
Comparison of the numbers of mutated genes in exonic regions, and ratio to total mutations detected by WES in 11 EBV+ DLBCL cases according to age and pathological subtype.
Fig 3.
An overview of the data analysis strategy for single-nucleotide variations (SNVs) and indels shown by whole-exome sequencing.
On average, we identified 220 (range, 126–358) somatically acquired point mutations per case. Of these, an average of 168 (range, 105–252) were non-synonymous and 81 (range, 52–149) were synonymous. Thus, the ratio of non-synonymous to synonymous was 2.08 (0.95–2.67) mutations per Mb.
Fig 4.
Signatures of mutational processes and intratumor clonal heterogeneity of EBV+ DLBCL cases.
The DeconstructSigs method was applied, which uncovered four mutational signatures (Fig 4A), including signatures 3, 5, 12, and 30. Among these signatures, signature 3 was the main type. MATH scores were used to evaluate intratumor clonal heterogeneity (Fig 4B), revealing allele frequency distribution values of between 47 and 86 for the tumors.
Table 4.
Relationship between clinical variables and MATH scores and OS in 11 EBV+ DLBCL cases.
Fig 5.
The 30 most commonly mutated genes from selected variants in EBV+ DLBCL identified by whole-exome sequencing.
Based on the total number of all mutation loci within one somatic mutated gene in a detected region (exonic region, intronic region, intergenic region, UTR, and other regions), the top 5 most frequently mutated genes were MUC16, PRSS3, MUC19, MUC3A, and RLIM in decreasing order.