Deletion lengthening at chromosomes 6q and 16q targets multiple tumor suppressor genes and is associated with an increasingly poor prognosis in prostate cancer.
Deletion lengthening at chromosomes 6q and 16q targets multiple tumor suppressor genes and is associated with an increasingly poor prognosis in prostate cancer.
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DOI：
10.18632/oncotarget.22408
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发表时间：
2017-12-12
期刊：
影响因子：
--
通讯作者：
Simon R
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文献类型：
--
作者：
Kluth M;Jung S;Habib O;Eshagzaiy M;Heinl A;Amschler N;Masser S;Mader M;Runte F;Barow P;Frogh S;Omari J;Möller-Koop C;Hube-Magg C;Weischenfeldt J;Korbel J;Steurer S;Krech T;Huland H;Graefen M;Minner S;Sauter G;Schlomm T;Simon R
前列腺癌的特征在于大小可以有很大变化的复发性缺失。我们假设大的缺失从小的缺失发展而来，这种“缺失延长”可能通过多个下调基因的组合效应具有“本身”致癌作用。体外敲除位于6 q12-q22缺失区域内的37个基因，鉴定出4个具有累加肿瘤抑制作用的基因，进一步支持了缺失大小对癌症侵袭性的作用。利用荧光原位杂交分析前列腺癌组织微阵列，我们确定了3,000多个肿瘤中6 q和16 q的缺失大小。16 q和6 q缺失长度与不良临床结果密切相关，如果将两种缺失的长度组合，这种影响甚至更强。为了研究癌症进展中的缺失延长，我们最终分析了来自317名患者的整个癌症的6 q和16 q缺失长度异质性，发现缺失在50-60%的6 q和16 q缺失癌症中扩展。总之，这些数据表明连续的“缺失延长”是前列腺癌进展的关键机制，导致具有肿瘤抑制特性的基因的平行下调，其中一些协同作用。
Prostate cancer is characterized by recurrent deletions that can considerably vary in size. We hypothesized that large deletions develop from small deletions and that this “deletion lengthening” might have a “per se” carcinogenic role through a combinatorial effect of multiple down regulated genes. In vitro knockdown of 37 genes located inside the 6q12-q22 deletion region identified 4 genes with additive tumor suppressive effects, further supporting a role of the deletion size for cancer aggressiveness. Employing fluorescence in-situ hybridization analysis on prostate cancer tissue microarrays, we determined the deletion size at 6q and 16q in more than 3,000 tumors. 16q and 6q deletion length was strongly linked to poor clinical outcome and this effect was even stronger if the length of both deletions was combined. To study deletion lengthening in cancer progression we eventually analyzed the entire cancers from 317 patients for 6q and 16q deletion length heterogeneity and found that the deletion expanded within 50-60% of 6q and 16q deleted cancers. Taken together, these data suggest continuous “deletion lengthening” as a key mechanism for prostate cancer progression leading to parallel down regulation of genes with tumor suppressive properties, some of which act cooperatively.
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DOI：
10.1042/bj20111502
发表时间：
2012-03-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Barkess G;Postnikov Y;Campos CD;Mishra S;Mohan G;Verma S;Bustin M;West KL
通讯作者：
West KL
影响因子：
64.5
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Elledge SJ
DOI：
10.1126/science.1219580
发表时间：
2012-07-06
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
Elledge SJ
DOI：
10.1126/science.1178124
发表时间：
2009-11-27
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Mani RS;Tomlins SA;Callahan K;Ghosh A;Nyati MK;Varambally S;Palanisamy N;Chinnaiyan AM
通讯作者：
Chinnaiyan AM
影响因子：
8
作者：
Huang S;Gulzar ZG;Salari K;Lapointe J;Brooks JD;Pollack JR
通讯作者：
Pollack JR