title: 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.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5176, USA.
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.forename: Z G
authors.initials: ZG
authors.lastname: Gulzar
authors.forename: K
authors.initials: K
authors.lastname: Salari
authors.forename: J
authors.initials: J
authors.lastname: Lapointe
authors.forename: J D
authors.initials: JD
authors.lastname: Brooks
authors.forename: J R
authors.initials: JR
authors.lastname: Pollack
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D055028:Comparative Genomic Hybridization; D004265:DNA Helicases / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering; D017384:Sequence Deletion
chemical_list: D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D004265:DNA Helicases; C080359:CHD1 protein, human