AUTHOR=Zhao Shankun , Xu Youwen , Wu Weizhou , Wang Pan , Wang Yichao , Jiang Hao , Zhu Jie 

TITLE=ARID1A Variations in Cholangiocarcinoma: Clinical Significances and Molecular Mechanisms

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.693295

DOI=10.3389/fonc.2021.693295

ISSN=2234-943X

ABSTRACT=<p>Cholangiocarcinoma (CCA), a high mortality malignant carcinoma characterized by advanced disease and frequent recurrence, constitutes a major challenge for treatment and prognosis. AT-rich interaction domain 1A (<italic>ARID1A</italic>) variation is a distinct genetic entity in CCA, getting mounting concerns recently. Here, we comprehensively reviewed the clinical significance and molecular mechanisms of <italic>ARID1A</italic> alterations in CCA. Based on the independent data derived from 29 relevant studies, the variation rate of <italic>ARID1A</italic> in intrahepatic and extrahepatic CCA is reported at 6.9–68.2% and 5–55%, respectively. Most of the included studies (28/29, 96.6%) suggest that <italic>ARID1A</italic> serves as a tumor suppressor in CCA. <italic>ARID1A</italic> variation may be an important prognostic indicator to predict disease mortality, metastasis, and recurrence in patients with CCA. Multifactorial molecular mechanisms are involved in the relationship between <italic>ARID1A</italic> variations and the pathogenesis and pathophysiology of CCA, including disruption of the cell cycle, chromatin remodeling, oxidative stress damage, DNA hypermethylation, and the interaction of multiple genes being affected. This review describes that <italic>ARID1A</italic> variation might be a potential diagnostic and prognostic biomarker for CCA. Future diagnoses and treatments targeting <italic>ARID1A</italic> hint towards a precision medicine strategy in the management of CCA.</p>