Experiments reveal how DNA-packaging protein mutation promotes breast cancer spread

A research team led by professor Chan Kui-ming from the Department of Biomedical Sciences at CityUHK discovered that H2BE113K, a missense H2B mutation, promotes colony formation and lung metastasis in breast cancer.

Recent research primarily investigated the effects of multiple H3 mutations on tumorigenesis, yet a significant number of H2B histone mutations have been identified in cancer patients. Chan and his team have previously identified the vital roles of H2BG53D and H2BE76K mutations in pancreatic cancer and breast cancer. This study focuses on H2BE113K, a histone H2B mutation identified predominantly in breast and lung cancers. It was published in Science Advances under the title “H2BE113K mutation promotes breast cancer metastasis through modulating chromatin dynamics.”

The research team used a CRISPR-Cas9 approach to generate H2BE113K knock-in breast cancer cells, revealing that this histone mutation had no effect on cell proliferation or cell migration, yet significantly enhanced the colony-forming ability of breast cancer cells. The team then performed RNA sequencing and CUT & RUN sequencing, identifying 221 candidate genes affected by H2BE113K. Some of these genes, including RAD50 and G3BP2, have been implicated in various cancers.

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