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The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts

BACKGROUND: Mutations in genes that are part of the splicing machinery for myelodysplastic syndromes (MDS), including MDS without ring sideroblasts (RS), have been widely investigated. The effects of these mutations on clinical outcomes have been diverse and contrasting. METHODS: We examined a cohor...

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Autores principales: Kang, Min-Gu, Kim, Hye-Ran, Seo, Bo-Young, Lee, Jun Hyung, Choi, Seok-Yong, Kim, Soo-Hyun, Shin, Jong-Hee, Suh, Soon-Pal, Ahn, Jae-Sook, Shin, Myung-Geun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483202/
https://www.ncbi.nlm.nih.gov/pubmed/26115659
http://dx.doi.org/10.1186/s12885-015-1493-5
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author Kang, Min-Gu
Kim, Hye-Ran
Seo, Bo-Young
Lee, Jun Hyung
Choi, Seok-Yong
Kim, Soo-Hyun
Shin, Jong-Hee
Suh, Soon-Pal
Ahn, Jae-Sook
Shin, Myung-Geun
author_facet Kang, Min-Gu
Kim, Hye-Ran
Seo, Bo-Young
Lee, Jun Hyung
Choi, Seok-Yong
Kim, Soo-Hyun
Shin, Jong-Hee
Suh, Soon-Pal
Ahn, Jae-Sook
Shin, Myung-Geun
author_sort Kang, Min-Gu
collection PubMed
description BACKGROUND: Mutations in genes that are part of the splicing machinery for myelodysplastic syndromes (MDS), including MDS without ring sideroblasts (RS), have been widely investigated. The effects of these mutations on clinical outcomes have been diverse and contrasting. METHODS: We examined a cohort of 129 de novo MDS patients, who did not harbor RS, for mutations affecting three spliceosomal genes (SF3B1, U2AF1, and SRSF2). RESULTS: The mutation rates of SF3B1, U2AF1, and SRSF2 were 7.0 %, 7.8 %, and 10.1 %, respectively. Compared with previously reported results, these rates were relatively infrequent. The SRSF2 mutation strongly correlated with old age (P < 0.001), while the mutation status of SF3B1 did not affect overall survival (OS), progression-free survival (PFS), or acute myeloid leukemia (AML) transformation. In contrast, MDS patients with mutations in U2AF1 or SRSF2 exhibited inferior PFS. The U2AF1 mutation was associated with inferior OS in low-risk MDS patients (P = 0.035). The SRSF2 mutation was somewhat associated with AML transformation (P = 0.083). CONCLUSION: Our findings suggest that the frequencies of the SF3B1, U2AF1, and SRSF2 splicing gene mutations in MDS without RS were relatively low. We also demonstrated that the U2AF1 and SRSF2 mutations were associated with an unfavorable prognostic impact in MDS patients without RS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1493-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-44832022015-06-28 The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts Kang, Min-Gu Kim, Hye-Ran Seo, Bo-Young Lee, Jun Hyung Choi, Seok-Yong Kim, Soo-Hyun Shin, Jong-Hee Suh, Soon-Pal Ahn, Jae-Sook Shin, Myung-Geun BMC Cancer Research Article BACKGROUND: Mutations in genes that are part of the splicing machinery for myelodysplastic syndromes (MDS), including MDS without ring sideroblasts (RS), have been widely investigated. The effects of these mutations on clinical outcomes have been diverse and contrasting. METHODS: We examined a cohort of 129 de novo MDS patients, who did not harbor RS, for mutations affecting three spliceosomal genes (SF3B1, U2AF1, and SRSF2). RESULTS: The mutation rates of SF3B1, U2AF1, and SRSF2 were 7.0 %, 7.8 %, and 10.1 %, respectively. Compared with previously reported results, these rates were relatively infrequent. The SRSF2 mutation strongly correlated with old age (P < 0.001), while the mutation status of SF3B1 did not affect overall survival (OS), progression-free survival (PFS), or acute myeloid leukemia (AML) transformation. In contrast, MDS patients with mutations in U2AF1 or SRSF2 exhibited inferior PFS. The U2AF1 mutation was associated with inferior OS in low-risk MDS patients (P = 0.035). The SRSF2 mutation was somewhat associated with AML transformation (P = 0.083). CONCLUSION: Our findings suggest that the frequencies of the SF3B1, U2AF1, and SRSF2 splicing gene mutations in MDS without RS were relatively low. We also demonstrated that the U2AF1 and SRSF2 mutations were associated with an unfavorable prognostic impact in MDS patients without RS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1493-5) contains supplementary material, which is available to authorized users. BioMed Central 2015-06-27 /pmc/articles/PMC4483202/ /pubmed/26115659 http://dx.doi.org/10.1186/s12885-015-1493-5 Text en © Kang et al. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Kang, Min-Gu
Kim, Hye-Ran
Seo, Bo-Young
Lee, Jun Hyung
Choi, Seok-Yong
Kim, Soo-Hyun
Shin, Jong-Hee
Suh, Soon-Pal
Ahn, Jae-Sook
Shin, Myung-Geun
The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts
title The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts
title_full The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts
title_fullStr The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts
title_full_unstemmed The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts
title_short The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts
title_sort prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483202/
https://www.ncbi.nlm.nih.gov/pubmed/26115659
http://dx.doi.org/10.1186/s12885-015-1493-5
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