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M. Taguchi et al.
demonstrated no significant difference in survival time between A-bomb survivors with MDS and unexposed MDS patients,13,14 which could be partly explained by their similar frequency of TP53 mutations. Taken together, these findings suggest that the profile of gene mutations in MDS among proximally exposed survivors is different to that of de novo MDS patients (reduction or lack of TET2 mutations in PE cases) and t-MDS patients (fewer TP53 mutations in PE cases).
A study on mutations of RUNX1 in MDS among A-bomb survivors (both proximally and distally exposed cases) in Hiroshima noted an increased alteration rate of 46% (6 out of 13 cases) and a missense/frameshift muta- tion rate of 31% (4 out of 13 cases).19 In the present study,
however, 3 out of 35 cases (8.6%) had RUNX1 mutations, which was as frequent as reported for de novo MDS (approx. 10%). There is no clear explanation for this dif- ference in the frequency of RUNX1 mutations but the small number of cases examined in each study (13 cases in the Hiroshima study, and 35 cases in this study) might have played a role. It is also possible that the differences in MDS subtypes influenced the results between two studies, as RUNX1 mutations are enriched in high-risk MDS.3 In the Hiroshima study, among 13 patients ana- lyzed, there were one patient with refractory anemia with excess blasts (RAEB), eight with RAEB in transformation (RAEB-t), and one AML, sharing 76.9% (10 out of 13) by MDS with increased blasts. Our patient cohort contained
Figure 2. Pattern of nucleotide sub- stitutions in the whole genomes of three patients in the proximally exposed group. The pattern of nucleotide substitution was exam- ined in three patients in the proximal- ly exposed group who were analyzed using whole genome sequencing. Frequencies of each pattern of sub- stitution are represented on the y- axis.
Figure 3. Somatic mutations in myelodysplastic syndromes (MDS) among A-bomb survivors. Each row and column represents a mutated gene and patient, respectively. Identified gene mutations are shown as blue (proximally exposed group) or yellow (distally exposed group) squares. Assumed functional path- ways are shown on the far left. UPN: unique patient number; ENT: entered within a 2 km radius from the hypocenter within two weeks after the atomic bombing. RCUD: refracto- ry cytopenia with uni-lineage dyspla- sia; RCMD: RC with multi-lineage dys- plasia; RAEB: refractory anemia with excess blasts; ICUS: idiopathic cytopenia of undetermined signifi- cance; AML: acute myeloid leukemia. DE: distally exposed group; PE: prox- imally exposed group.
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haematologica | 2020; 105(2)