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タイトル: | Recurrent genetic defects on chromosome 5q in myeloid neoplasms |
著者: | Hosono, Naoko Makishima, Hideki https://orcid.org/0000-0001-5983-8578 (unconfirmed) Mahfouz, Reda Przychodzen, Bartlomiej Yoshida, Kenichi Jerez, Andres LaFramboise, Thomas Polprasert, Chantana Clemente, Michael J. Shiraishi, Yuichi Chiba, Kenichi Tanaka, Hiroko Miyano, Satoru Sanada, Masashi Cui, Edward Verma, Amit K. McDevit, Michael A. List, Alan F. Saunthararajah, Yogen Sekeres, Mikkael A. Boultwood, Jacqueline Ogawa, Seishi Maciejewski, Jaroslaw P. |
著者名の別形: | 吉田, 健一 真田, 昌 小川, 誠司 |
キーワード: | MDS del(5q) TP53 G3BP1 |
発行日: | 2017 |
出版者: | Impact Journals, LLC |
誌名: | Oncotarget |
巻: | 8 |
号: | 4 |
開始ページ: | 6483 |
終了ページ: | 6495 |
抄録: | [Background]: Deletion of chromosome 5q (del(5q)) is the most common karyotypic abnormality in myeloid neoplasms. [Materials and Methods]: To define the pathogenic molecular features associated with del(5q), next–generation sequencing was applied to 133 patients with myeloid neoplasms (MDS; N = 69, MDS/MPN; N = 5, sAML; N = 29, pAML; N = 30) with del(5q) as a sole abnormally or a part of complex karyotype and results were compared to molecular features of patients diploid for chr5. [Findings]: A number of 5q genes with haploinsufficient expression and/or recurrent somatic mutations were identified; for these genes, CSNK1A1 and G3BP1 within the commonly deleted 5q region and DDX41 within a commonly retained region were most commonly affected by somatic mutations. These genes showed consistent haploinsufficiency in deleted cases; low expression/mutations of G3BP1 or DDX41 were associated with poor survival, likely due to decreased cellular function. The most common mutations on other chromosomes in patients with del(5q) included TP53, and mutations of FLT3 (ITD or TKD), NPM1 or TET2 and were mutually exclusive. Serial sequencing allowed for definition of clonal architecture and dynamics, in patients with exome sequencing allelic imbalance for informative SNPs facilitated simultaneous approximation of clonal size of del(5q) and clonal burden for somatic mutations. [Interpretation]: Our results illuminate the spectrum of molecular defects characteristic of del(5q), their clinical impact and succession of stepwise evolution. |
著作権等: | All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. |
URI: | http://hdl.handle.net/2433/227671 |
DOI(出版社版): | 10.18632/oncotarget.14130 |
PubMed ID: | 28031539 |
出現コレクション: | 学術雑誌掲載論文等 |
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