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

## TL;DR

A new mutation in the CHD4 gene is linked to a rare case of breast cancer that spreads to the bones and responds to hormone therapy.

## Contribution

A novel CHD4 truncation mutation is identified in occult breast cancer with bone metastases, not previously reported in other cancers.

## Key findings

- The CHD4 p.Trp736Ter mutation disrupts ATPase activity and NuRD complex assembly.
- The cancer was classified as luminal-A subtype and showed response to endocrine therapy.
- The mutation may shift CHD4's regulatory balance, promoting metastatic progression.

## 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.