Mutational analysis of Polycomb genes in solid tumours identifies <i>PHC3</i> amplification as a possible cancer-driving genetic alteration.

Abstract

Background: Polycomb group genes (PcGs) are epigenetic effectors implicated in most cancer hallmarks. The mutational status of all PcGs has never been systematically assessed in solid tumours. Methods: We conducted a multi-step analysis on publically available databases and patient samples to identify somatic aberrations of PcGs. Results: Data from more than 1000 cancer patients show for the first time that the PcG member PHC3 is amplified in three epithelial neoplasms (rate: 8–35%). This aberration predicts poorer prognosis in lung and uterine carcinomas (Po0.01). Gene amplification correlates with mRNA overexpression (Po0.01), suggesting a functional role of this aberration. Conclusion: PHC3 amplification may emerge as a biomarker and potential therapeutic target in a relevant fraction of epithelial tumours