# A unified model for Duchenne muscular dystrophy gene involvement in cancer: context‐dependent tumour suppression and oncogenicity

## TL;DR

This study shows that the DMD gene, known for causing Duchenne muscular dystrophy, can act as both a tumor suppressor and an oncogene depending on the cancer type.

## Contribution

The paper introduces a unified, context-dependent model for DMD's dual role in cancer.

## Key findings

- High DMD expression is linked to improved or worsened survival outcomes depending on cancer type.
- The Dp71ab transcript mirrors total DMD trends and distinguishes two tumor groups with opposing survival associations.
- Divergent DMD effects may be linked to signaling and adhesion-related DAPC components.

## Abstract

Evidence implicates the Duchenne muscular dystrophy gene (DMD) in tumorigenesis, but survival trends are inconsistent. To resolve this, we conducted a comprehensive global analysis of DMD expression and survival outcomes across 33 tumour types using bulk RNA sequencing data from The Cancer Genome Atlas. We examined the impact of total DMD, individual transcript and dystrophin‐associated protein complex (DAPC) gene expression levels on overall survival using Kaplan–Meier analysis, Cox proportional hazard modelling and pathway analysis. DMD expression was significantly associated with survival in nine cancers after Bonferroni correction (α = 0.0015), with high expression linked to either improved or worsened outcomes depending on cancer type. The most abundant DMD transcript, Dp71ab, mirrored total DMD trends, distinguishing two tumour groups with opposing survival associations. Hierarchical clustering suggests these divergent effects may be linked to a subset of signalling and adhesion‐related DAPC components. Our findings indicate that DMD does not act uniformly as an oncogene or tumour suppressor. Instead, we propose a context‐dependent dual model whereby high DMD expression is tumour suppressive in aggressive cancers and oncogenic in less aggressive tumours.

We propose a context‐dependent model where the Duchenne muscular dystrophy (DMD) gene acts as a tumour suppressor in aggressive tumours and as an oncogene in less aggressive ones. We propose this model as a unified framework to explain the opposing survival associations with DMD expression and to guide experimental exploration of the dual role of DMD in cancer.