Work

Case Report: Novel mutation in CHD4 triggers occult breast cancer with bone metastases

Year: 2025

Type: article

Abstract: Chromatin domain-binding protein 4 (CHD4), the ATPase core component of the NuRD complex, exerts dual roles in epigenetic regulation-mediating both gene silencing and activation. We report a case of occult breast cancer with extensive bone metastasis harboring a novel somatic truncation mutation in the catalytic SNF2 domain (CHD4 p.Trp736Ter). This mutation, unreported in other cancers to date, abolishes ATPase activity and disrupts NuRD complex assembly. Multimodal analysis (PET/CT, biomarkers, pathology) confirmed the case as luminal-A subtype and revealed a significant response to endocrine therapy. We hypothesize that this CHD4 mutation may alter the protein's dual regulatory balance, particularly enhancing its potential gene-activating functions, and propose that impaired chromatin remodeling driven by such mutations is associated with metastatic progression of breast cancer.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2025.1682794

Authors: Hang Dong, Jingtong Zhao, Boyin Zhang, Xiaowen Wu, Guangyao Liu

Institutions: Jilin University, Peking University, Peking University Cancer Hospital

Language: English

Topic: Chromatin Remodeling and Cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801