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


CONCLUSIONS
PHC3 amplification may emerge as a biomarker and potential therapeutic target in a relevant fraction of epithelial tumours.
Experimental Therapeutics, BC Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
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D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000235:genetics; D057890:Epigenomics; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*
C519295:PHC3 protein, human; D012333:RNA, Messenger; D063150:Polycomb Repressive Complex 1