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Recurrent deletion of CHD1 in prostate cancer with relevance to cell invasiveness

Abstract

Though prostate cancer is often indolent, it is nonetheless a leading cause of cancer death. Defining the underlying molecular genetic alterations may lead to new strategies for prevention or treatment. Towards this goal, we performed array-based comparative genomic hybridization (CGH) on 86 primary prostate tumors. Among the most frequent alterations not associated with a known cancer gene, we identified focal deletions within 5q21 in 15 out of 86 (17%) cases. By high-resolution tiling array CGH, the smallest common deletion targeted just one gene, the chromatin remodeler chromodomain helicase DNA-binding protein 1 (CHD1). Expression of CHD1 was significantly reduced in tumors with deletion (P=0.03), and compared with normal prostate (P=0.04). Exon sequencing analysis also uncovered nonsynonymous mutations in 1 out of 7 (14%) cell lines (LAPC4) and in 1 out of 24 (4%) prostate tumors surveyed. RNA interference-mediated knockdown of CHD1 in two nontumorigenic prostate epithelial cell lines, OPCN2 and RWPE-1, did not alter cell growth, but promoted cell invasiveness, and in OPCN2-enhanced cell clonogenicity. Taken together, our findings suggest that CHD1 deletion may underlie cell invasiveness in a subset of prostate cancers, and indicate a possible novel role of altered chromatin remodeling in prostate tumorigenesis.

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Acknowledgements

We wish to thank the members of the Pollack lab for helpful discussion. Supported by grants from the NIH (CA122246 to JRP; CA111782 to JDB; CA130472 to SH), the Burroughs Wellcome Fund (1007519 to JRP), the American Cancer Society (PF-08-078-01-MGO to SH), Prostate Cancer Canada (to JL) and the Stanford Cancer Center (to JRP).

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Correspondence to J R Pollack.

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Huang, S., Gulzar, Z., Salari, K. et al. Recurrent deletion of CHD1 in prostate cancer with relevance to cell invasiveness. Oncogene 31, 4164–4170 (2012). https://doi.org/10.1038/onc.2011.590

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