Mutational and expressional analyses of STAG2 gene in solid cancers

Area of Science:

• Molecular biology
• Cancer research
• Genetics

Background:

• Aneuploidy is a hallmark of cancer, contributing to tumor development.
• The STAG2 gene provides instructions for making a protein component of the cohesin complex, essential for accurate chromosome segregation during cell division.
• Previous studies indicated STAG2 gene mutations and protein loss in glioblastoma, Ewing's sarcoma, and melanoma.

Purpose of the Study:

• To investigate the frequency of STAG2 gene alterations in various common carcinomas.
• To determine if STAG2 protein loss is a common event in gastric carcinoma (GC), colorectal carcinoma (CRC), and prostate carcinoma (PCA).

Main Methods:

• Analyzed STAG2 somatic mutations in 45 GC, 45 CRC, 45 breast carcinomas, 45 non-small cell lung cancers, and 45 prostate carcinomas (PCA) using single-strand conformation polymorphism.
• Assessed STAG2 protein expression in 100 GC, 103 CRC, and 107 PCA tissues via immunohistochemistry.
• Compared STAG2 expression in tumor tissues with corresponding normal epithelial cells.

Main Results:

• STAG2 protein was highly expressed in normal gastric, colon, and prostate epithelial cells.
• Loss of STAG2 protein expression was observed in 27% of GC, 23% of CRC, and 30% of PCA.
• No STAG2 gene mutations were detected in the analyzed carcinomas, despite significant protein loss.

Conclusions:

• Loss of STAG2 protein expression is a frequent event in GC, CRC, and PCA, irrespective of cancer subtype, stage, or grade.
• The data suggest that STAG2 protein downregulation, rather than somatic mutation, is a common mechanism for STAG2 inactivation in these carcinomas.
• STAG2 inactivation through protein loss may contribute to aneuploidy and cancer development in these tumor types.