STAG2, or Stromal Antigen 2, is a gene that plays a role in various cellular processes. It is a component of the cohesin complex, which is essential for maintaining genetic integrity. Understanding its normal function helps explain what happens when it malfunctions, especially in disease. It is involved in several biological functions that maintain cell health.
The Core Function of STAG2
The STAG2 gene codes for a protein that is a subunit of the cohesin complex. This complex forms a ring-shaped structure holding DNA strands together. This cohesion is significant during cell division, ensuring each new cell receives a complete set of chromosomes. Without proper STAG2 function, chromosomes might not separate correctly, leading to an uneven distribution of genetic material in daughter cells.
STAG2 also contributes to other cellular activities. It is involved in DNA repair, helping to fix damaged DNA. STAG2 also influences gene expression, the process where genetic information creates functional products. This impacts how cells develop and respond to their environment, highlighting the gene’s broad influence.
STAG2’s Role in Cancer
Mutations in the STAG2 gene are frequently observed in cancers, suggesting its role as a tumor suppressor. Loss of STAG2 function due to mutations can lead to chromosome instability and uncontrolled cell growth. This disruption in normal cellular processes can contribute to tumor development and progression.
STAG2 mutations are common in cancers such as bladder cancer, glioblastoma, and Ewing sarcoma. In bladder cancer, mutations are more frequent in non-muscle invasive forms. While STAG2 typically acts as a tumor suppressor, its expression in muscle-invasive bladder cancer has sometimes been associated with more aggressive characteristics.
In glioblastoma, a severe type of brain cancer, STAG2 mutations are frequently found. STAG2-mutant glioblastoma cells may become more sensitive to chemotherapy drugs that induce DNA double-strand breaks. In Ewing sarcoma, a bone and soft tissue cancer affecting children and young adults, STAG2 loss-of-function mutations are linked to increased aggressiveness and a poorer prognosis. These mutations can alter how genes are expressed, contributing to the disease’s progression.
STAG2 and Other Health Conditions
Beyond its connection to cancer, STAG2 mutations are also associated with a group of developmental disorders known as cohesinopathies. These conditions arise from errors in the cohesin complex, of which STAG2 is a part. Cohesinopathies are rare multisystem developmental disorders that can present with a variety of symptoms.
Individuals with cohesinopathies experience intellectual disability, growth delays, and distinctive facial features. For example, increased levels of STAG2 due to gene duplication have been linked to a cohesinopathy characterized by intellectual disability and behavioral problems. This demonstrates that both the loss and gain of STAG2 function can lead to health issues, particularly impacting neurodevelopment and overall growth.
Impact on Diagnosis and Therapy
Understanding STAG2’s role has practical implications for diagnosing and treating certain diseases. Identifying STAG2 mutations can serve as a diagnostic marker in some cancers. For instance, in papillary non-muscle-invasive bladder cancer, STAG2 status may help predict the risk of recurrence and progression. Tumors with intact STAG2 expression have shown a higher likelihood of recurrence compared to STAG2-deficient tumors.
The presence or absence of functional STAG2 also presents opportunities for developing targeted therapies. In cancers with STAG2 mutations, such as glioblastoma and Ewing sarcoma, cells may exhibit increased sensitivity to DNA-damaging agents, including certain chemotherapies and PARP inhibitors. This vulnerability arises because STAG2 plays a role in DNA repair, and its dysfunction makes cells more reliant on other repair pathways, which can then be therapeutically targeted. Research is ongoing to explore these vulnerabilities and develop new treatment strategies that leverage STAG2’s altered function in disease.