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  3. Anatomy and Cell Biology / 解剖學暨細胞生物學研究所
  4. Loss of SFRP1 expression is a key progression event in gastrointestinal stromal tumor pathogenesis
 
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Loss of SFRP1 expression is a key progression event in gastrointestinal stromal tumor pathogenesis

Journal
Human Pathology
Journal Volume
107
Pages
69-79
Date Issued
2021
Author(s)
Liang C.-W.
CHING-YAO YANG  
Flavin R.
Fletcher J.A.
TZU-PIN LU  
I-RUE LAI  
Li Y.-I.
YIH-LEONG CHANG  
JEN-CHIEH LEE  
DOI
10.1016/j.humpath.2020.10.010
URI
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85097043697&doi=10.1016%2fj.humpath.2020.10.010&partnerID=40&md5=7c436a8230cf5c7e857d0cc4edf0beed
https://scholars.lib.ntu.edu.tw/handle/123456789/551016
Abstract
The mechanism of high-grade transformation in gastrointestinal stromal tumors (GISTs) remains to be clarified. We aim to discover the key progression events by studying biphasic GISTs. The study group included 101 GISTs. Nineteen of these had been screened from 263 GISTs to represent the early stage of GIST high-grade transformation, characterized by juxtaposed low-grade and high-grade regions in the same tumor (so-called biphasic GISTs). Mutational analyses, fluorescence in situ hybridization (FISH), NanoString analyses, telomere analysis, and gene expression profiling were carried out, followed by in silico analyses, cell line study, and immunohistochemical validation. Using gene expression analysis, downregulation of SFRP1 was revealed to be the main event in GIST high-grade transformation (p = 0.013), accompanied by upregulation of EZH2. In silico analyses revealed that downregulation of SFRP1 was a common feature in GIST progression across several different series. Immunohistochemically, the expression of SFRP1 was validated to be significantly lower in high-grade GISTs (WHO risk group 3a or higher) than in low-grade GISTs (p < 0.001), and attenuation/loss of SFRP1 was associated with GIST tumor progression (p < 0.001). By NanoString and FISH analyses, chromosomal 9/9p loss was the only recurrent large-scale chromosome aberration in biphasic GISTs, with a correlation with SFRP1 downregulation. Subclones containing chromosome 9/9p loss could be appreciated in the low-grade parts of biphasic GISTs. TP53 mutation, RB1 loss, KIT/PDGFRA mutation, and alternative lengthening of telomeres did not play a significant role in GIST high-grade transformation. In conclusion, high-grade transformation of GISTs features SFRP1 downregulation and chromosome 9/9p loss.
Subjects
CDKN2A
Gastrointestinal stromal tumor
NanoString
SFRP1
p16(INK4a)
SDGs

[SDGs]SDG3

Other Subjects
cyclin dependent kinase inhibitor 2A; platelet derived growth factor alpha receptor; protein p53; retinoblastoma protein; secreted frizzled related protein 1; stem cell factor receptor; transcription factor EZH2; EZH2 protein, human; membrane protein; SFR
Publisher
W.B. Saunders
Type
journal article

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