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Title: Recurrent genetic defects on chromosome 5q in myeloid neoplasms
Authors: Hosono, Naoko
Makishima, Hideki  kyouindb  KAKEN_id  orcid 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  kyouindb  KAKEN_id
Maciejewski, Jaroslaw P.
Author's alias: 吉田, 健一
真田, 昌
小川, 誠司
Keywords: MDS
del(5q)
TP53
G3BP1
Issue Date: 2017
Publisher: Impact Journals, LLC
Journal title: Oncotarget
Volume: 8
Issue: 4
Start page: 6483
End page: 6495
Abstract: [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.
Rights: 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(Published Version): 10.18632/oncotarget.14130
PubMed ID: 28031539
Appears in Collections:Journal Articles

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