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C.R. Bolen et al.
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Figure 1. Frequently observed gene alterations in patients with diffuse large B-cell lymphoma (DLBCL) in the GOYA trial (clinicaltrials.gov identifier: NCT01287741). (A) Most frequently (≥2% of cases) observed gene alterations: single nucleotide variant (SNV), amplifications and deletions. (B) Genes with significant differences in mutation rates* between the activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCL subtypes. (C) Frequency of BCL2 and CDKN2A alterations in the ABC and GCB DLBCL subtypes. *False discovery rate (FDR) <0.05. CNA: copy number abnormality; trans: translocation.
chemotherapy cycles, and geographic region. Multiple testing adjustment was performed by estimating false discovery rates (FDR) using the Benjamini-Hochberg procedure (significance <5% FDR).
Results
Baseline disease characteristics were similar between patients with NGS available and the overall GOYA ITT population, except for race (Online Supplementary Table S1) and geographic region (data not shown) due to lack of access to samples from China.
Genomic alterations detectable by targeted next-generation sequencing
Of 465 sequenced genes, 59 (13%) were identified as functionally altered (i.e. having mutations that significant-
ly alter the function of a gene in a manner that has been previously reported to drive cancer progression) in at least 10 of 499 patient samples (≥2% prevalence), and 334 addi- tional genes with alterations were identified in ≥1 patient; 3% of patients had no identified mutation. The median number of gene alterations per patient was 6 (range 0-17). The median number of single nucleotide variants (SNV) and copy number abnormalities (CNA) per patient were 4 (range, 0-16) and 0 (range, 0-10), respectively. Ninety- seven percent of cases harbored ≥1 alteration and 93% of cases harbored multiple (≥2) alterations.
The most frequently (≥2% cases) observed gene alter- ations (SNV, amplifications and deletions) are shown in Figure 1A. SNV were the most common mutation type, while CNA were specific to a few genes, including CDKN2A/B and REL. Of the 31 analyzed gene rearrange- ments, BCL2, MYC and BCL6 were the most frequently rearranged; for these genes, the most frequently observed
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haematologica | 2020; 105(9)