Recurrent deletion of CHD1 in prostate cancer with relevance to cell invasiveness.
Recurrent deletion of CHD1 in prostate cancer with relevance to cell invasiveness.
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DOI：
10.1038/onc.2011.590
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发表时间：
2012-09-13
期刊：
影响因子：
8
通讯作者：
Pollack JR
中科院分区：
文献类型：
--
作者：
Huang S;Gulzar ZG;Salari K;Lapointe J;Brooks JD;Pollack JR
虽然前列腺癌通常是无痛的，但它仍然是癌症死亡的主要原因。确定潜在的分子遗传改变可能会导致新的预防或治疗策略。为此，我们对86例原发性前列腺肿瘤进行了基于阵列的比较基因组杂交（CGH）。在与已知癌症基因无关的最常见的改变中，我们在86例病例中的15例（17%）中发现了5 q21内的局灶性缺失。通过高分辨率平铺阵列CGH，最小的共同缺失仅针对一个基因，染色质重塑染色体结构域解旋酶DNA结合蛋白1（CHD 1）。CHD 1在缺失型前列腺癌中的表达显著低于正常前列腺组织（P= 0.04），缺失型前列腺癌中CHD 1的表达显著低于正常前列腺组织（P= 0.03）。外显子测序分析还发现了7个细胞系中的1个（14%）（LAPC 4）和24个前列腺肿瘤中的1个（4%）的非同义突变。RNA干扰介导的敲除CHD 1在两个非致瘤性前列腺上皮细胞系，OPCN 2和RWPE-1，没有改变细胞生长，但促进细胞侵袭力，并在OPCN 2增强细胞克隆形成。综上所述，我们的研究结果表明，CHD 1缺失可能是前列腺癌细胞侵袭性的基础，并表明染色质重塑改变在前列腺肿瘤发生中可能的新作用。
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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影响因子：
50.3
作者：
Taylor BS;Schultz N;Hieronymus H;Gopalan A;Xiao Y;Carver BS;Arora VK;Kaushik P;Cerami E;Reva B;Antipin Y;Mitsiades N;Landers T;Dolgalev I;Major JE;Wilson M;Socci ND;Lash AE;Heguy A;Eastham JA;Scher HI;Reuter VE;Scardino PT;Sander C;Sawyers CL;Gerald WL
通讯作者：
Gerald WL
DOI：
10.1016/j.mrfmmm.2006.07.012
发表时间：
2007-05-01
影响因子：
2.3
作者：
Marfella, Concetta G. A.;Imbalzano, Anthony N.
通讯作者：
Imbalzano, Anthony N.
DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
64.8
作者：
Gaspar-Maia A;Alajem A;Polesso F;Sridharan R;Mason MJ;Heidersbach A;Ramalho-Santos J;McManus MT;Plath K;Meshorer E;Ramalho-Santos M
通讯作者：
Ramalho-Santos M
影响因子：
--
作者：
Menon, Tushar;Yates, Joel A.;Bochar, Daniel A.
通讯作者：
Bochar, Daniel A.