TY - JOUR
T1 - Dynamics of clonal evolution in myelodysplastic syndromes
AU - Makishima, Hideki
AU - Yoshizato, Tetsuichi
AU - Yoshida, Kenichi
AU - Sekeres, Mikkael A.
AU - Radivoyevitch, Tomas
AU - Suzuki, Hiromichi
AU - Przychodzen, Bartlomie J.
AU - Nagata, Yasunobu
AU - Meggendorfer, Manja
AU - Sanada, Masashi
AU - Okuno, Yusuke
AU - Hirsch, Cassandra
AU - Kuzmanovic, Teodora
AU - Sato, Yusuke
AU - Sato-Otsubo, Aiko
AU - Laframboise, Thomas
AU - Hosono, Naoko
AU - Shiraishi, Yuichi
AU - Chiba, Kenichi
AU - Haferlach, Claudia
AU - Kern, Wolfgang
AU - Tanaka, Hiroko
AU - Shiozawa, Yusuke
AU - Gómez-Seguí, Inés
AU - Husseinzadeh, Holleh D.
AU - Thota, Swapna
AU - Guinta, Kathryn M.
AU - Dienes, Brittney
AU - Nakamaki, Tsuyoshi
AU - Miyawaki, Shuichi
AU - Saunthararajah, Yogen
AU - Chiba, Shigeru
AU - Miyano, Satoru
AU - Shih, Lee Yung
AU - Haferlach, Torsten
AU - Ogawa, Seishi
AU - MacIejewski, Jaroslaw P.
N1 - Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature.
PY - 2017/1/31
Y1 - 2017/1/31
N2 - To elucidate differential roles of mutations in myelodysplastic syndromes (MDS), we investigated clonal dynamics using whole-exome and/or targeted sequencing of 699 patients, of whom 122 were analyzed longitudinally. Including the results from previous reports, we assessed a total of 2,250 patients for mutational enrichment patterns. During progression, the number of mutations, their diversity and clone sizes increased, with alterations frequently present in dominant clones with or without their sweeping previous clones. Enriched in secondary acute myeloid leukemia (sAML; in comparison to high-risk MDS), FLT3, PTPN11, WT1, IDH1, NPM1, IDH2 and NRAS mutations (type 1) tended to be newly acquired, and were associated with faster sAML progression and a shorter overall survival time. Significantly enriched in high-risk MDS (in comparison to low-risk MDS), TP53, GATA2, KRAS, RUNX1, STAG2, ASXL1, ZRSR2 and TET2 mutations (type 2) had a weaker impact on sAML progression and overall survival than type-1 mutations. The distinct roles of type-1 and type-2 mutations suggest their potential utility in disease monitoring.
AB - To elucidate differential roles of mutations in myelodysplastic syndromes (MDS), we investigated clonal dynamics using whole-exome and/or targeted sequencing of 699 patients, of whom 122 were analyzed longitudinally. Including the results from previous reports, we assessed a total of 2,250 patients for mutational enrichment patterns. During progression, the number of mutations, their diversity and clone sizes increased, with alterations frequently present in dominant clones with or without their sweeping previous clones. Enriched in secondary acute myeloid leukemia (sAML; in comparison to high-risk MDS), FLT3, PTPN11, WT1, IDH1, NPM1, IDH2 and NRAS mutations (type 1) tended to be newly acquired, and were associated with faster sAML progression and a shorter overall survival time. Significantly enriched in high-risk MDS (in comparison to low-risk MDS), TP53, GATA2, KRAS, RUNX1, STAG2, ASXL1, ZRSR2 and TET2 mutations (type 2) had a weaker impact on sAML progression and overall survival than type-1 mutations. The distinct roles of type-1 and type-2 mutations suggest their potential utility in disease monitoring.
UR - https://www.scopus.com/pages/publications/85006365447
U2 - 10.1038/ng.3742
DO - 10.1038/ng.3742
M3 - 文章
C2 - 27992414
AN - SCOPUS:85006365447
SN - 1061-4036
VL - 49
SP - 204
EP - 212
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -
SDG3 健康與福祉