Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Idiopathic hypereosinophilia is clonal disorder? Clonality identified by targeted sequencingopen access

Authors
Lee, Jee-SooSeo, HeewonIm, KyongokPark, Si NaeKim, Sung-MinLee, Eun KyoungKim, Jung-AhLee, Joon-heeKwon, SunghoonKim, MiyoungKoh, InsongHwang, SeungwooPark, Heung-WooKang, Hye-RyunPark, Kyoung SooKim, Ju HanLee, Dong Soon
Issue Date
Oct-2017
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v.12, no.10, pp.1 - 17
Indexed
SCIE
SCOPUS
Journal Title
PLOS ONE
Volume
12
Number
10
Start Page
1
End Page
17
URI
https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/151552
DOI
10.1371/journal.pone.0185602
ISSN
1932-6203
Abstract
Idiopathic hypereosinophilia (IHE)/idiopathic hypereosinophilic syndrome (IHES) has been defined by a persistent elevation of the blood eosinophil count exceeding 1.5x10(3)/mu L, without evidence of reactive or clonal causes. While T-cell clonality assessment has been recommended for unexplained hypereosinophilia, this approach is not often applied to routine practice in the clinic. We hypothesized that the clonality would exist in a subset of IHE/IHES patients. We aimed to investigate the candidate mutations and T-cell clonality in IHE/IHES and to explore the role of mutations in eosinophil proliferation. We performed targeted capture sequencing for 88 genes using next-generation sequencing, T-cell receptor (TCR) gene rearrangement assays, and pathway network analysis in relation to eosinophil proliferation. By targeted sequencing, 140 variants in 59 genes were identified. Sixteen out of 30 patients (53.3%) harbored at least one candidate mutation. The most frequently affected genes were NOTCH1 (26.7%), SCRIB and STAG2 (16.7%), and SH2B3 (13.3%). Network analysis revealed that our 21 candidate genes (BIRC3, BRD4, CSF3R, DNMT3A, EGR2, EZH2, FAT4, FLT3, GATA2, IKZF, JAK2, MAPK1, MPL, NF1, NOTCH1, PTEN, RB1, RUNX1, TET2, TP53 and WT1) are functionally linked to the eosinophilopoietic pathway. Among the 21 candidate genes, five genes (MAPK1, RUNX1, GATA2, NOTCH1 and TP53) with the highest number of linkages were considered major genes. A TCR assay revealed that four patients (13.3%) had a clonal TCR rearrangement. NOTCH1 was the most frequently mutated gene and was shown to be a common node for eosinophilopoiesis in our network analysis, while the possibility of hidden T cell malignancy was indwelling in the presence of NOTCH1 mutation, though not revealed by aberrant T cell study. Collectively, these results provide new evidence that mutations affecting eosinophilopoiesis underlie a subset of IHE/IHES, and the candidate genes are inferred to act their potential roles in the eosino-philopoietic pathway.
Files in This Item
Appears in
Collections
서울 의과대학 > 서울 생리학교실 > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Koh, In Song photo

Koh, In Song
COLLEGE OF MEDICINE (DEPARTMENT OF PHYSIOLOGY)
Read more

Altmetrics

Total Views & Downloads

BROWSE