Genome analysis of myelodysplastic syndromes among atomic bomb survivors in Nagasaki

• Published in: Haematologica (Roma) Vol. 105; no. 2; pp. 358 - 365
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.02.2020
• Subjects: Atomic Bomb Survivors; Chromosome Aberrations; Humans; Myelodysplastic Syndromes - etiology; Myelodysplastic Syndromes - genetics; Risk Factors; Survivors
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2019.219386

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 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 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 were significantly more frequent in proximally exposed group with mutations identified on the remaining allele in 2 out of 5 cases. , 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 origin. Considering the role of in DNA damage response after radiation exposure, further studies are warranted to elucidate how 11q deletion and aberrations of contribute to the pathogenesis of MDS after radiation exposure.