| Literature DB >> 27992414 |
Hideki Makishima1,2, Tetsuichi Yoshizato2, Kenichi Yoshida2, Mikkael A Sekeres1,3, Tomas Radivoyevitch1, Hiromichi Suzuki2, Bartlomiej Przychodzen1, Yasunobu Nagata2, Manja Meggendorfer4, Masashi Sanada5, Yusuke Okuno2, Cassandra Hirsch1, Teodora Kuzmanovic1, Yusuke Sato2, Aiko Sato-Otsubo2, Thomas LaFramboise6, Naoko Hosono1, Yuichi Shiraishi7, Kenichi Chiba7, Claudia Haferlach5, Wolfgang Kern5, Hiroko Tanaka7, Yusuke Shiozawa2, Inés Gómez-Seguí1, Holleh D Husseinzadeh1, Swapna Thota1, Kathryn M Guinta1, Brittney Dienes1, Tsuyoshi Nakamaki8, Shuichi Miyawaki9, Yogen Saunthararajah1, Shigeru Chiba10, Satoru Miyano7, Lee-Yung Shih11, Torsten Haferlach5, Seishi Ogawa2, Jaroslaw P Maciejewski1.
Abstract
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.Entities:
Mesh：
Year: 2016 PMID： 27992414 PMCID： PMC8210656 DOI： 10.1038/ng.3742
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330