Dynamics of clonal evolution in myelodysplastic syndromes

作者：Makishima Hideki; Yoshizato Tetsuichi; Yoshida Kenichi; Sekeres Mikkael A; Radivoyevitch Tomas; Suzuki Hiromichi; Przychodzen Bartlomiej; Nagata Yasunobu; Meggendorfer Manja; Sanada Masashi; Okuno Yusuke; Hirsch Cassandra; Kuzmanovic Teodora; Sato Yusuke; Sato Otsubo Aiko; LaFramboise Thomas; Hosono Naoko; Shiraishi Yuichi; Chiba Kenichi; Haferlach Claudia; Kern Wolfgang; Tanaka Hiroko; Shiozawa Yusuke; Gomez Segui Ines; Husseinzadeh Holleh D; Thota Swapna

来源：Nature Genetics, 2017, 49(2): 204-212.

DOI：10.1038/ng.3742

To elucidate differential roles of mutations in myelodysplastic syndromes (MDS), we investigated clonal dynamics using wholeexome 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.

• 出版日期2017-2
• 单位河北医科大学; 长春大学