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Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance

The aim of this study was to profile the spectrum of genetic mutations in acute myeloid leukemia (AML) patients co-occurring with CEBPA double mutation (CEBPA(dm)). Between January 1, 2012, and June 30, 2017, 553 consecutive patients with de novo AML were screened for CEBPA mutations. Out of these,...

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Autores principales: Su, Long, Tan, YeHui, Lin, Hai, Liu, XiaoLiang, Yu, Li, Yang, YanPing, Liu, ShanShan, Bai, Ou, Yang, Yan, Jin, FengYan, Sun, JingNan, Liu, ChunShui, Liu, QiuJu, Gao, SuJun, Li, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5982761/
https://www.ncbi.nlm.nih.gov/pubmed/29861846
http://dx.doi.org/10.18632/oncotarget.23873
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author Su, Long
Tan, YeHui
Lin, Hai
Liu, XiaoLiang
Yu, Li
Yang, YanPing
Liu, ShanShan
Bai, Ou
Yang, Yan
Jin, FengYan
Sun, JingNan
Liu, ChunShui
Liu, QiuJu
Gao, SuJun
Li, Wei
author_facet Su, Long
Tan, YeHui
Lin, Hai
Liu, XiaoLiang
Yu, Li
Yang, YanPing
Liu, ShanShan
Bai, Ou
Yang, Yan
Jin, FengYan
Sun, JingNan
Liu, ChunShui
Liu, QiuJu
Gao, SuJun
Li, Wei
author_sort Su, Long
collection PubMed
description The aim of this study was to profile the spectrum of genetic mutations in acute myeloid leukemia (AML) patients co-occurring with CEBPA double mutation (CEBPA(dm)). Between January 1, 2012, and June 30, 2017, 553 consecutive patients with de novo AML were screened for CEBPA mutations. Out of these, 81 patients classified as CEBPA(dm) were analyzed further by a sensitive next-generation sequencing assay for mutations in 112 candidate genes. Within the CEBPA gene itself, we found 164 mutations. The most common mutated sites were c.936_937insGAG (n = 11/164, 6.71%) and c.939_940insAAG (n = 11/164, 6.71%), followed by c.68dupC (n = 10/164, 6.10%). The most common co-occurring mutations were found in the CSF3R (n = 16/81, 19.75%), WT1 (n = 15/81, 18.52%), and GATA2 (n = 13/81, 16.05%) genes. Patients with CSF3R mutations had an inferior four-year relapse-free survival (RFS) than those with the wild-type gene (15.3% versus 46.8%, respectively; P = 0.021). Patients with WT1 mutations had an inferior five-year RFS compared with those without such mutations (0% versus 26.6%, respectively, P = 0.003). However, GATA2, CSF3R, WT1 mutations had no significant influence on the overall survival. There were some differences in the location of mutational hotspots within the CEBPA gene, as well as hotspots of other co-occurring genetic mutations, between AML patients from Chinese and Caucasian populations. Some co-occurring mutations may be potential candidates for refining the prognoses of AML patients with CEBPA(dm) in the Chinese population.
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spelling pubmed-59827612018-06-01 Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance Su, Long Tan, YeHui Lin, Hai Liu, XiaoLiang Yu, Li Yang, YanPing Liu, ShanShan Bai, Ou Yang, Yan Jin, FengYan Sun, JingNan Liu, ChunShui Liu, QiuJu Gao, SuJun Li, Wei Oncotarget Research Paper The aim of this study was to profile the spectrum of genetic mutations in acute myeloid leukemia (AML) patients co-occurring with CEBPA double mutation (CEBPA(dm)). Between January 1, 2012, and June 30, 2017, 553 consecutive patients with de novo AML were screened for CEBPA mutations. Out of these, 81 patients classified as CEBPA(dm) were analyzed further by a sensitive next-generation sequencing assay for mutations in 112 candidate genes. Within the CEBPA gene itself, we found 164 mutations. The most common mutated sites were c.936_937insGAG (n = 11/164, 6.71%) and c.939_940insAAG (n = 11/164, 6.71%), followed by c.68dupC (n = 10/164, 6.10%). The most common co-occurring mutations were found in the CSF3R (n = 16/81, 19.75%), WT1 (n = 15/81, 18.52%), and GATA2 (n = 13/81, 16.05%) genes. Patients with CSF3R mutations had an inferior four-year relapse-free survival (RFS) than those with the wild-type gene (15.3% versus 46.8%, respectively; P = 0.021). Patients with WT1 mutations had an inferior five-year RFS compared with those without such mutations (0% versus 26.6%, respectively, P = 0.003). However, GATA2, CSF3R, WT1 mutations had no significant influence on the overall survival. There were some differences in the location of mutational hotspots within the CEBPA gene, as well as hotspots of other co-occurring genetic mutations, between AML patients from Chinese and Caucasian populations. Some co-occurring mutations may be potential candidates for refining the prognoses of AML patients with CEBPA(dm) in the Chinese population. Impact Journals LLC 2018-01-03 /pmc/articles/PMC5982761/ /pubmed/29861846 http://dx.doi.org/10.18632/oncotarget.23873 Text en Copyright: © 2018 Su et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Su, Long
Tan, YeHui
Lin, Hai
Liu, XiaoLiang
Yu, Li
Yang, YanPing
Liu, ShanShan
Bai, Ou
Yang, Yan
Jin, FengYan
Sun, JingNan
Liu, ChunShui
Liu, QiuJu
Gao, SuJun
Li, Wei
Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance
title Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance
title_full Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance
title_fullStr Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance
title_full_unstemmed Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance
title_short Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance
title_sort mutational spectrum of acute myeloid leukemia patients with double cebpa mutations based on next-generation sequencing and its prognostic significance
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5982761/
https://www.ncbi.nlm.nih.gov/pubmed/29861846
http://dx.doi.org/10.18632/oncotarget.23873
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