TY - JOUR
T1 - The high frequency of the U2AF1 S34Y mutation and its association with isolated trisomy 8 in myelodysplastic syndrome in Asians, but not in Caucasians
AU - Kim, Seon Young
AU - Kim, Kwantae
AU - Hwang, Byungjin
AU - Im, Kyongok
AU - Park, Si Nae
AU - Kim, Jung Ah
AU - Hwang, Sang Mee
AU - Bang, Duhee
AU - Lee, Dong Soon
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/10
Y1 - 2017/10
N2 - Mutational profiles of 153 Korean myelodysplastic syndrome (MDS) patients were investigated. Sequencing of 87 genes presented similar mutational profiles in Korean MDS patients compared with previous reports. The most frequently mutated genes were ASXL1 (22.9%), U2AF1 (16.3%), TP53 (13.7%), RUNX1 (10.5%), TET2 (10.5%), DNMT3A (8.5%), and SRSF2 (8.5%). The U2AF1 mutation frequency was higher, with different frequencies in the mutated sites of U2AF1 (S34Y, 6/25; S34F, 11/25; and Q157P 8/25). The U2AF1 S34Y mutation was strongly associated with isolated trisomy 8 (5/6, 83%) and was characterized by a younger age of MDS onset (median, 39 years). The S34F mutation was associated with trisomy 8 (6/11, 55%) and del(20q) (3/11, 27%). Data from 10 literatures (total 3460 patients) of 229 U2AF1-mutated cases revealed a significant association between the S34Y and trisomy 8 in Asians (P = 0.0001), but not in Caucasians (P = 0.080). We infer that U2AF1 S34 mutations characterize a distinct subgroup of MDS: younger age of onset and differential associations with particular cytogenetic aberrations depending on specific mutations [S34Y to +8; S34F to +8 and del(20q)]. The impact and causal relationship between U2AF1 S34 and trisomy 8 need to be elucidated, which might contribute to design of tailored treatments.
AB - Mutational profiles of 153 Korean myelodysplastic syndrome (MDS) patients were investigated. Sequencing of 87 genes presented similar mutational profiles in Korean MDS patients compared with previous reports. The most frequently mutated genes were ASXL1 (22.9%), U2AF1 (16.3%), TP53 (13.7%), RUNX1 (10.5%), TET2 (10.5%), DNMT3A (8.5%), and SRSF2 (8.5%). The U2AF1 mutation frequency was higher, with different frequencies in the mutated sites of U2AF1 (S34Y, 6/25; S34F, 11/25; and Q157P 8/25). The U2AF1 S34Y mutation was strongly associated with isolated trisomy 8 (5/6, 83%) and was characterized by a younger age of MDS onset (median, 39 years). The S34F mutation was associated with trisomy 8 (6/11, 55%) and del(20q) (3/11, 27%). Data from 10 literatures (total 3460 patients) of 229 U2AF1-mutated cases revealed a significant association between the S34Y and trisomy 8 in Asians (P = 0.0001), but not in Caucasians (P = 0.080). We infer that U2AF1 S34 mutations characterize a distinct subgroup of MDS: younger age of onset and differential associations with particular cytogenetic aberrations depending on specific mutations [S34Y to +8; S34F to +8 and del(20q)]. The impact and causal relationship between U2AF1 S34 and trisomy 8 need to be elucidated, which might contribute to design of tailored treatments.
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U2 - 10.1016/j.leukres.2017.09.001
DO - 10.1016/j.leukres.2017.09.001
M3 - Article
C2 - 28938223
AN - SCOPUS:85029487039
SN - 0145-2126
VL - 61
SP - 96
EP - 103
JO - Leukemia Research
JF - Leukemia Research
ER -