Recurrent mechanisms of biallelic epigenetic inactivation reveal new putative tumour suppressor genes in prostate cancer.

Biallelic epigenetic inactivation of ZFHX3 occurs at a recurrence rate comparable to TP53 in prostate cancer, promoting oncogene upregulation and metastasis.

• Why it matters: Understanding how tumour suppressor genes are inactivated in prostate cancer is crucial, especially when large genomic losses obscure their identification. This knowledge can improve detection of key drivers and therapeutic targets.
• What they did: The authors developed Epi2Hit, a computational method integrating genome sequencing, epigenomics, and gene expression data, and applied it to 2,021 prostate cancer samples to identify biallelic inactivation events.
• The result: They found that epigenetic silencing of ZFHX3, often combined with genomic loss, leads to increased oncogene activity and faster metastasis, highlighting epigenetic mechanisms as critical in tumour suppressor inactivation.