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Genome analysis of myelodysplastic syndromes among atomic bomb survivors in Nagasaki
Ionizing radiation is a risk factor for myeloid neoplasms including myelodysplastic syndromes (MDS), and atomic bomb survivors have been shown to have a significantly higher risk of MDS. Our previous analyses demonstrated that MDS among these survivors had a significantly higher frequency of complex...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ferrata Storti Foundation
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012461/ https://www.ncbi.nlm.nih.gov/pubmed/31101757 http://dx.doi.org/10.3324/haematol.2019.219386 |
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author | Taguchi, Masataka Mishima, Hiroyuki Shiozawa, Yusuke Hayashida, Chisa Kinoshita, Akira Nannya, Yasuhito Makishima, Hideki Horai, Makiko Matsuo, Masatoshi Sato, Shinya Itonaga, Hidehiro Kato, Takeharu Taniguchi, Hiroaki Imanishi, Daisuke Imaizumi, Yoshitaka Hata, Tomoko Takenaka, Motoi Moriuchi, Yukiyoshi Shiraishi, Yuichi Miyano, Satoru Ogawa, Seishi Yoshiura, Koh-ichiro Miyazaki, Yasushi |
author_facet | Taguchi, Masataka Mishima, Hiroyuki Shiozawa, Yusuke Hayashida, Chisa Kinoshita, Akira Nannya, Yasuhito Makishima, Hideki Horai, Makiko Matsuo, Masatoshi Sato, Shinya Itonaga, Hidehiro Kato, Takeharu Taniguchi, Hiroaki Imanishi, Daisuke Imaizumi, Yoshitaka Hata, Tomoko Takenaka, Motoi Moriuchi, Yukiyoshi Shiraishi, Yuichi Miyano, Satoru Ogawa, Seishi Yoshiura, Koh-ichiro Miyazaki, Yasushi |
author_sort | Taguchi, Masataka |
collection | PubMed |
description | Ionizing radiation is a risk factor for myeloid neoplasms including myelodysplastic syndromes (MDS), and atomic bomb survivors have been shown to have a significantly higher risk of MDS. Our previous analyses demonstrated that MDS among these survivors had a significantly higher frequency of complex karyotypes and structural alterations of chromosomes 3, 8, and 11. However, there was no difference in the median survival time between MDS among survivors compared with those of de novo origin. This suggested that a different pathophysiology may underlie the causative genetic aberrations for those among survivors. In this study, we performed genome analyses of MDS among survivors and found that proximally exposed patients had significantly fewer mutations in genes such as TET2 along the DNA methylation pathways, and they had a significantly higher rate of 11q deletions. Among the genes located in the deleted portion of chromosome 11, alterations of ATM were significantly more frequent in proximally exposed group with mutations identified on the remaining allele in 2 out of 5 cases. TP53, which is frequently mutated in therapy-related myeloid neoplasms, was equally affected between proximally and distally exposed patients. These results suggested that the genetic aberration profiles in MDS among atomic bomb survivors differed from those in therapy-related and de novo origin. Considering the role of ATM in DNA damage response after radiation exposure, further studies are warranted to elucidate how 11q deletion and aberrations of ATM contribute to the pathogenesis of MDS after radiation exposure. |
format | Online Article Text |
id | pubmed-7012461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ferrata Storti Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-70124612020-02-20 Genome analysis of myelodysplastic syndromes among atomic bomb survivors in Nagasaki Taguchi, Masataka Mishima, Hiroyuki Shiozawa, Yusuke Hayashida, Chisa Kinoshita, Akira Nannya, Yasuhito Makishima, Hideki Horai, Makiko Matsuo, Masatoshi Sato, Shinya Itonaga, Hidehiro Kato, Takeharu Taniguchi, Hiroaki Imanishi, Daisuke Imaizumi, Yoshitaka Hata, Tomoko Takenaka, Motoi Moriuchi, Yukiyoshi Shiraishi, Yuichi Miyano, Satoru Ogawa, Seishi Yoshiura, Koh-ichiro Miyazaki, Yasushi Haematologica Article Ionizing radiation is a risk factor for myeloid neoplasms including myelodysplastic syndromes (MDS), and atomic bomb survivors have been shown to have a significantly higher risk of MDS. Our previous analyses demonstrated that MDS among these survivors had a significantly higher frequency of complex karyotypes and structural alterations of chromosomes 3, 8, and 11. However, there was no difference in the median survival time between MDS among survivors compared with those of de novo origin. This suggested that a different pathophysiology may underlie the causative genetic aberrations for those among survivors. In this study, we performed genome analyses of MDS among survivors and found that proximally exposed patients had significantly fewer mutations in genes such as TET2 along the DNA methylation pathways, and they had a significantly higher rate of 11q deletions. Among the genes located in the deleted portion of chromosome 11, alterations of ATM were significantly more frequent in proximally exposed group with mutations identified on the remaining allele in 2 out of 5 cases. TP53, which is frequently mutated in therapy-related myeloid neoplasms, was equally affected between proximally and distally exposed patients. These results suggested that the genetic aberration profiles in MDS among atomic bomb survivors differed from those in therapy-related and de novo origin. Considering the role of ATM in DNA damage response after radiation exposure, further studies are warranted to elucidate how 11q deletion and aberrations of ATM contribute to the pathogenesis of MDS after radiation exposure. Ferrata Storti Foundation 2020-02 /pmc/articles/PMC7012461/ /pubmed/31101757 http://dx.doi.org/10.3324/haematol.2019.219386 Text en Copyright© 2020 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher. |
spellingShingle | Article Taguchi, Masataka Mishima, Hiroyuki Shiozawa, Yusuke Hayashida, Chisa Kinoshita, Akira Nannya, Yasuhito Makishima, Hideki Horai, Makiko Matsuo, Masatoshi Sato, Shinya Itonaga, Hidehiro Kato, Takeharu Taniguchi, Hiroaki Imanishi, Daisuke Imaizumi, Yoshitaka Hata, Tomoko Takenaka, Motoi Moriuchi, Yukiyoshi Shiraishi, Yuichi Miyano, Satoru Ogawa, Seishi Yoshiura, Koh-ichiro Miyazaki, Yasushi Genome analysis of myelodysplastic syndromes among atomic bomb survivors in Nagasaki |
title | Genome analysis of myelodysplastic syndromes among atomic bomb survivors in Nagasaki |
title_full | Genome analysis of myelodysplastic syndromes among atomic bomb survivors in Nagasaki |
title_fullStr | Genome analysis of myelodysplastic syndromes among atomic bomb survivors in Nagasaki |
title_full_unstemmed | Genome analysis of myelodysplastic syndromes among atomic bomb survivors in Nagasaki |
title_short | Genome analysis of myelodysplastic syndromes among atomic bomb survivors in Nagasaki |
title_sort | genome analysis of myelodysplastic syndromes among atomic bomb survivors in nagasaki |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012461/ https://www.ncbi.nlm.nih.gov/pubmed/31101757 http://dx.doi.org/10.3324/haematol.2019.219386 |
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