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Aberration of ARID1A Is Associated With the Tumorigenesis and Prognosis of Sporadic Nonfunctional Pancreatic Neuroendocrine Tumors.

Authors :
Han X
Chen W
Chen P
Zhou W
Rong Y
Lv Y
Li JA
Ji Y
Chen W
Lou W
Xu X
Source :
Pancreas [Pancreas] 2020 Apr; Vol. 49 (4), pp. 514-523.
Publication Year :
2020

Abstract

Objective: The genetic aberrations that underlie chromatin remodeling in sporadic nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) remain largely unknown. Here, we investigated the dysregulation of the switch/sucrose nonfermentable (SWI/SNF) component ARID1A and its correlation with clinicopathological features and prognosis.<br />Methods: We sequenced the exomes of sporadic NF-pNETs. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to determine messenger RNA level and protein expression.<br />Results: The sporadic NF-pNETs harbored 264 somatic mutations in 228 different genes, most commonly affecting the SWI/SNF components ARID1B (57.1%) and ARID1A (42.9%). The expression of ARID1A was remarkably downregulated in NF-pNETs and corresponding liver metastases compared with that in normal pancreatic islet tissue. Reduced expression of ARID1A was associated with malignant clinicopathological features (P < 0.05). The loss of ARID1A was related to a high Ki-67 index (P < 0.05). Patients with ARID1A-negative expression had a significantly worse overall survival rate than those with ARID1A-positive expression (P < 0.05). The ARID1A status was an independent predictor of overall survival, and a nomogram integrating ARID1A with clinicopathological features was proposed.<br />Conclusions: The loss of SWI/SNF components ARID1A may be associated with malignant behaviors and an unfavorable prognosis. Aberrations of ARID1A may contribute to tumorigenesis and metastasis in sporadic NF-pNETs.

Details

Language :
English
ISSN :
1536-4828
Volume :
49
Issue :
4
Database :
MEDLINE
Journal :
Pancreas
Publication Type :
Academic Journal
Accession number :
32282764
Full Text :
https://doi.org/10.1097/MPA.0000000000001535