Diagnostic significance and prognostic role of the ARID1A gene in cancer outcomes (Review)

Abstract

Mutations of the ARID1A gene, which encodes the basic directional subunit of SWI/SNF chromatin remodeling complexes, were detected in the middle of the last decade in several cancerous tissue types, highlighting its tumour-suppressive role. Since then, functional studies of the homologous protein have indicated that through its interactions with nucleosomal DNA, transcription factors and nuclear hormone receptors, it plays a key role in regulating cellular proliferation, gene expression and the repair of genetic material, while the loss of its expression triggers carcinogenesis, through mechanisms which have not yet been elucidated. This bibliographic review of clinical investigations focused on the detection of ARID1A mutations and expression levels in malignant tumours, as well as on their association with the prognosis of ARID1A-deficient patients exhibiting a high degree of heterogeneity in the corresponding research findings. The clarification of the prognostic significance of the gene requires further investigation, focusing on cancers and patients of common clinicopathological features. Contents1. Introduction 2. Summary of the materials and methods used for analysis in previous studies 3. Summary of the findings of previous studies regarding ARID1A in cancer 4. Discussion 5. Conclusion and future therapeutic perspectives

Circulating Tumor Cell and Metabolites as Novel Biomarkers for Early-Stage Lung Cancer Diagnosis

“…There are still some problems to be solved, such as the target genes regulated by ARID1A and the specific mechanisms in tumor suppression, whether other signaling pathways can exert tumor suppression effects, and the prognostic value of ARID1A and patients. This requires comprehensive and in-depth research (34). Our study is the first to find IGF2 and RTCH1 mutations in peripheral blood CTC NGS of early lung cancer.…”

The Molecular Landscape of Primary Acral Melanoma: A Multicenter Study of the Italian Melanoma Intergroup (IMI)

“…Among TWT samples, ARID1A mutations were found in three cases suggesting an important role in AM oncogenesis. ARID1A is a core member of the switch/sucrose non-fermentable (SWI/SNF) chromatin-remodeling complex, a machinery that provides the access of proteins to DNA, and its mutations have been frequently reported in many different types of cancers [ 32 , 33 ]. The pathogenicity of ARID1A mutations in melanoma was already reported in previous studies and aberrations in this pathway seem to occur in about 20% of AMs [ 19 , 34 , 35 ].…”

Exploiting vulnerabilities of SWI/SNF chromatin remodelling complexes for cancer therapy

“…The BAF subunit ARID1A binds DNA non-specifically via its AT-rich interactive DNA-binding domain and has the highest mutation frequency among BAF subunits in cancer [ 42 ]. ARID1A acts as a tumour suppressor, and loss of function has been associated with tumour development in ovarian carcinoma [ 43 ], pancreatic cancer [ 44 ] and cervical cancer [ 45 ].…”

“…ARID1A acts as a tumour suppressor, and loss of function has been associated with tumour development in ovarian carcinoma [ 43 ], pancreatic cancer [ 44 ] and cervical cancer [ 45 ]. Interestingly, the cancer mutations are spread across almost all regions of the ARID1A gene and do not cluster in the DNA-binding domain as seen in transcription factors such as p53 [ 42 , 46 ]. One reason for this is that ARID1A is involved in many subunit–subunit contacts stabilising the base module of the complex that are susceptible to inactivating mutations.…”

“…One reason for this is that ARID1A is involved in many subunit–subunit contacts stabilising the base module of the complex that are susceptible to inactivating mutations. Loss of ARID1A tumour suppressive functions triggers cancer development through perturbations of DNA-damage response and cell-cycle pathways [ 42 ]. Furthermore, several studies have also demonstrated that an ARID1A loss is associated with activation of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and a concurrent loss of PTEN expression, which both activate the PI3K/AKT/mTOR cell-cycle pathway [ 47 – 50 ].…”