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Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome

To investigate the U2AF1 gene mutation site, mutation load and co-mutations genes in patients with myelodysplastic syndrome (MDS) and their effects on prognosis. Gene mutation detection by next-generation sequence and related clinical data of 234 MDS patients were retrospectively collected and analy...

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Autores principales: Wang, Haiqiong, Guo, Yongbo, Dong, Zhenkun, Li, Tao, Xie, Xinsheng, Wan, Dingming, Jiang, Zhongxing, Yu, Jifeng, Guo, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596495/
https://www.ncbi.nlm.nih.gov/pubmed/33122737
http://dx.doi.org/10.1038/s41598-020-74744-z
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author Wang, Haiqiong
Guo, Yongbo
Dong, Zhenkun
Li, Tao
Xie, Xinsheng
Wan, Dingming
Jiang, Zhongxing
Yu, Jifeng
Guo, Rong
author_facet Wang, Haiqiong
Guo, Yongbo
Dong, Zhenkun
Li, Tao
Xie, Xinsheng
Wan, Dingming
Jiang, Zhongxing
Yu, Jifeng
Guo, Rong
author_sort Wang, Haiqiong
collection PubMed
description To investigate the U2AF1 gene mutation site, mutation load and co-mutations genes in patients with myelodysplastic syndrome (MDS) and their effects on prognosis. Gene mutation detection by next-generation sequence and related clinical data of 234 MDS patients were retrospectively collected and analyzed for the relationship between the clinical characteristics, treatment efficacy and prognosis of U2AF1 gene mutation. Among the 234 MDS patients, the U2AF1 gene mutation rate was 21.7% (51 cases), and the median variant allele frequency was 39.5%. Compared with the wild type, the U2AF1 mutant had a higher incidence of chromosome 8 aberration, and was positively correlated with the occurrence of ASXL1, RUNX1, SETBP1 gene mutation, negatively correlated with SF3B1, NPM1 genes mutation (p < 0.05). The most common mutation site of U2AF1 was S34F (32 cases), while U2AF1 Q157P site mutations had a higher incidence of chromosome 7 abnormalities (p = 0.003). The U2AF1 gene mutation more frequently coincided with signal pathway related gene mutations (p = 0.043) with a trend of shortened overall survival. Among patients with U2AF1 gene mutations, those with ASXL1 mutations were prone to develop into acute myeloid leukemia, those with RUNX1 mutations had an increased risk of relapse, and those with TET2 mutations had higher 1-year survival rate. Compared with the patient group of lower mutation load (VAF ≤ 40%), the group with higher mutation load of U2AF1 (VAF > 40%) had a significantly lower 1-year survival rate (46.1% and 80.5%, p = 0.027). The criteria of U2AF1 VAF > 40% is an independent indicator for poor prognosis of MDS patients. VAF > 40% of U2AF1 is an independent factor of short OS in MDS patients. MDS patients with a mutation in the Q157P site of U2AF1 and a higher U2AF1 mutation load suggests poor prognosis, and co-mutated genes in U2AF1 can affect disease progression and prognosis.
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spelling pubmed-75964952020-10-30 Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome Wang, Haiqiong Guo, Yongbo Dong, Zhenkun Li, Tao Xie, Xinsheng Wan, Dingming Jiang, Zhongxing Yu, Jifeng Guo, Rong Sci Rep Article To investigate the U2AF1 gene mutation site, mutation load and co-mutations genes in patients with myelodysplastic syndrome (MDS) and their effects on prognosis. Gene mutation detection by next-generation sequence and related clinical data of 234 MDS patients were retrospectively collected and analyzed for the relationship between the clinical characteristics, treatment efficacy and prognosis of U2AF1 gene mutation. Among the 234 MDS patients, the U2AF1 gene mutation rate was 21.7% (51 cases), and the median variant allele frequency was 39.5%. Compared with the wild type, the U2AF1 mutant had a higher incidence of chromosome 8 aberration, and was positively correlated with the occurrence of ASXL1, RUNX1, SETBP1 gene mutation, negatively correlated with SF3B1, NPM1 genes mutation (p < 0.05). The most common mutation site of U2AF1 was S34F (32 cases), while U2AF1 Q157P site mutations had a higher incidence of chromosome 7 abnormalities (p = 0.003). The U2AF1 gene mutation more frequently coincided with signal pathway related gene mutations (p = 0.043) with a trend of shortened overall survival. Among patients with U2AF1 gene mutations, those with ASXL1 mutations were prone to develop into acute myeloid leukemia, those with RUNX1 mutations had an increased risk of relapse, and those with TET2 mutations had higher 1-year survival rate. Compared with the patient group of lower mutation load (VAF ≤ 40%), the group with higher mutation load of U2AF1 (VAF > 40%) had a significantly lower 1-year survival rate (46.1% and 80.5%, p = 0.027). The criteria of U2AF1 VAF > 40% is an independent indicator for poor prognosis of MDS patients. VAF > 40% of U2AF1 is an independent factor of short OS in MDS patients. MDS patients with a mutation in the Q157P site of U2AF1 and a higher U2AF1 mutation load suggests poor prognosis, and co-mutated genes in U2AF1 can affect disease progression and prognosis. Nature Publishing Group UK 2020-10-29 /pmc/articles/PMC7596495/ /pubmed/33122737 http://dx.doi.org/10.1038/s41598-020-74744-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Haiqiong
Guo, Yongbo
Dong, Zhenkun
Li, Tao
Xie, Xinsheng
Wan, Dingming
Jiang, Zhongxing
Yu, Jifeng
Guo, Rong
Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome
title Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome
title_full Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome
title_fullStr Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome
title_full_unstemmed Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome
title_short Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome
title_sort differential u2af1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596495/
https://www.ncbi.nlm.nih.gov/pubmed/33122737
http://dx.doi.org/10.1038/s41598-020-74744-z
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