H2ax, a histone H2A variant, is of great significance in maintaining genomic stability. When DNA double-strand breaks (DSBs) occur in higher eukaryotic cells, H2ax is promptly phosphorylated at Serine 139 to generate γ-H2ax. This phosphorylation event is activated by the phosphatidylinositol-3-OH-kinase-like family of protein kinases, including DNA-PKcs, ATM, and ATR. γ-H2ax then serves as a key site for the accumulation of components in the DNA damage signaling cascade [1].

The detection of γ-H2ax can potentially serve as a biomarker for the transformation of normal tissue to premalignant and malignant tissues. In various cancer types such as breast, endometrial, and other cancers, its prognostic value has been investigated. For example, in breast cancer, higher γ-H2ax values are associated with greater tumor size, higher grade, more affected lymph nodes, and are inversely related to estrogen and progesterone receptor levels [2,3].

In conclusion, H2ax phosphorylation, resulting in γ-H2ax, is a crucial event in the DNA damage response, playing a significant role in cancer development and progression. Studies on H2ax, especially through its phosphorylated form γ-H2ax, help in understanding the mechanisms of cancer formation, providing potential prognostic and therapeutic implications in cancer research.