Fig 1.
A schematic diagram showing individual coding exons and flanking intronic sequences affected by the identified CHEK2 sequence variants.
The most important structural/functional domains of CHK2 kinase are depicted by color bars [SQ/TQ domain (amino acid (aa) 19–69) in blue, FHA domain (aa 112–175) in yellow, and kinase domain (aa 220–486) in violet]. The left-hand side shows synonymous and intronic CHEK2 variants (italicized) while the right-hand side shows CHK2 protein structure-altering variants (frame-shift and missense) that were described in the NHL patients group (in red), controls (green) or in both populations (in black).
Table 1.
Clinical characteristics of NHL patients (N = 340) and DLBCL patients from the validation group (N = 186).
Table 2.
Germline alterations of the CHEK2 gene changing the CHK2 protein structure identified in NHL patients and controls with their frequencies and related odds ratios (OR).
Table 3.
Germline intronic and silent alterations in the CHEK2 gene in NHL patients and controls with their frequencies and related odds ratios (OR).
Fig 2.
Overall survival (OS; upper panels) and progression-free survival (PFS; lower panels) in all NHL patients (regardless of histology subtype) classified according to the type of CHEK2 alterations.
Panels show: A. the influence of all alterations affecting the CHK2 coding sequence (cds; HROS = 1.6; 95% CI 0.79–3.24 and HRPFS = 2.1; 95% CI 1.12–4.05); B. the influence of the I157T mutation (HROS = 1.5; 95% CI 0.62–3.70 and HRPFS = 3.7; 95% CI 1.42–9.43) and C. the influence of the c.319+43dupA variant (HROS = 0.8; 95% CI 0.50–1.15 and HRPFS = 0.6; 95% CI 0.44–0.89).
Fig 3.
Overall survival (OS; upper panels) and progression-free survival (PFS; lower panels) in DLBCL patients.
Panels show: A. the influence of all alterations affecting the CHK2 coding sequence (cds; HROS = 2.3; 95% CI 0.77–6.97 and HRPFS = 2.6; 95% CI 0.91–7.44); B. the influence of the I157T mutation (HROS = 2.9; 95% CI 0.70–12.00 and HRPFS = 5.2; 95% CI 1.25–22.16) and C. the influence of the c.319+43dupA variant (HROS = 0.6; 95% CI 0.32–0.97 and HRPFS = 0.5; 95% CI 0.32–0.86).