CHD1 Is a 5q21 Tumor Suppressor Required for ERG Rearrangement in Prostate Cancer

被引：179

作者：

Burkhardt, Lia ^{[1
]}

Fuchs, Sarah ^{[1
]}

Krohn, Antje ^{[1
]}

Masser, Sawinee ^{[1
]}

Mader, Malte ^{[1
]}

Kluth, Martina ^{[1
]}

Bachmann, Frederik ^{[1
]}

Huland, Hartwig ^{[2
,3
]}

Steuber, Thomas ^{[2
,3
]}

Graefen, Markus ^{[2
,3
]}

Schlomm, Thorsten ^{[2
,3
]}

Minner, Sarah ^{[1
]}

Sauter, Guido ^{[1
]}

Sirma, Hueseyin ^{[1
]}

Simon, Ronald ^{[1
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Inst Pathol, D-20246 Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Martini Clin, Prostate Canc Ctr, D-20246 Hamburg, Germany

[3] Univ Med Ctr Hamburg Eppendorf, Urol Clin, Sect Translat Prostate Canc Res, D-20246 Hamburg, Germany

来源：

CANCER RESEARCH | 2013年 / 73卷 / 09期

关键词：

GENES; PTEN; TRANSCRIPTION; ABERRATIONS; EXPRESSION; LANDSCAPE; DELETION; BINDING; PROTEIN; PML;

D O I：

10.1158/0008-5472.CAN-12-1342

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Deletions involving the chromosomal band 5q21 are among the most frequent alterations in prostate cancer. Using single-nucleotide polymorphism (SNP) arrays, we mapped a 1.3 megabase minimally deleted region including only the repulsive guidance molecule B (RGMB) and chromodomain helicase DNA-binding protein 1 (CHD1) genes. Functional analyses showed that CHD1 is an essential tumor suppressor. FISH analysis of 2,093 prostate cancers revealed a strong association between CHD1 deletion, prostate-specific antigen (PSA) biochemical failure (P = 0.0038), and absence of ERG fusion (P < 0.0001). We found that inactivation of CHD1 in vitro prevents formation of ERG rearrangements due to impairment of androgen receptor (AR)-dependent transcription, a prerequisite for ERG translocation. CHD1 is required for efficient recruitment of AR to responsive promoters and regulates expression of known AR-responsive tumor suppressor genes, including NKX3-1, FOXO1, and PPAR gamma. Our study establishes CHD1 as the 5q21 tumor suppressor gene in prostate cancer and shows a key role of this chromatin remodeling factor in prostate cancer biology. (C) 2013 AACR.

引用

页码：2795 / 2805

页数：11

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