CXorf67 in malignancies: Deciphering epigenetic landscapes and clinical implications for precision oncology

The emerging focus on epigenetic regulation in cancer biology has unveiled the significant role of CXorf67, a protein encoded by a gene on the X chromosome. CXorf67 interacts with core components of PRC2, namely EZH2 and SUZ12, thereby influencing histone modifications like H3K27me3. Research indicates that CXorf67 is overexpressed in specific malignancies, including posterior fossa ependymomas, diffuse midline glioma, endometrial stromal sarcoma, non-small cell lung cancer, and Merkel cell carcinoma. In posterior fossa ependymomas and diffuse midline glioma, CXorf67 mimics the oncogenic histone H3K27M, inhibiting PRC2 function and altering chromatin states. In endometrial stromal sarcoma, CXorf67 forms fusion genes with MBTD1, potentially disrupting polycomb group (PcG) functions. Additionally, CXorf67's interaction with PALB2 affects the BRCA1-PALB2-BRCA2 complex, influencing DNA repair mechanisms. These findings highlight CXorf67's dual role in epigenetic regulation and DNA damage response, suggesting its potential as a therapeutic target. However, further research is needed to explore its functions in other cancers and clarify its molecular mechanisms. Our review synthesizes current knowledge on CXorf67's biological significance, particularly in epigenetics and DNA damage, and its implications in oncogenesis.