Mutational analysis of Polycomb genes in solid tumours identifies PHC3 amplification as a possible cancer-driving genetic alteration

Br J Cancer. 2013 Sep 17;109(6):1699-702. doi: 10.1038/bjc.2013.454. Epub 2013 Aug 13.

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 (P<0.01). Gene amplification correlates with mRNA overexpression (P<0.01), 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.

MeSH terms

  • DNA Mutational Analysis
  • Endometrial Neoplasms / genetics
  • Epigenomics
  • Female
  • Gene Amplification
  • Humans
  • Lung Neoplasms / genetics
  • Male
  • Mutation
  • Neoplasms / genetics*
  • Polycomb Repressive Complex 1 / genetics*
  • Prognosis
  • RNA, Messenger / genetics*

Substances

  • PHC3 protein, human
  • RNA, Messenger
  • Polycomb Repressive Complex 1