Oliveira Andre M, Hsi Bae-Li, Weremowicz Stanislawa, Rosenberg Andrew E, Dal Cin Paola, Joseph Nora, Bridge Julia A, Perez-Atayde Antonio R, Fletcher Jonathan A
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Cancer Res. 2004 Mar 15;64(6):1920-3. doi: 10.1158/0008-5472.can-03-2827.
Aneurysmal bone cyst (ABC) is a locally aggressive osseous lesion that typically occurs during the first two decades of life. ABC was regarded historically as a nonneoplastic process, but recent cytogenetic data have shown clonal rearrangements of chromosomal bands 16q22 and 17p13, indicating a neoplastic basis in at least some ABCs. Herein we show that a recurring ABC chromosomal translocation t(16;17)(q22;p13) creates a fusion gene in which the osteoblast cadherin 11 gene (CDH11) promoter region on 16q22 is juxtaposed to the entire ubiquitin-specific protease USP6 (Tre2) coding sequence on 17p13. CDH11-USP6 fusion transcripts were demonstrated only in ABC with t(16;17) but other ABCs had CDH11 or USP6 rearrangements resulting from alternate cytogenetic mechanisms. CDH11 is expressed strongly in bone, and our findings implicate a novel oncogenic mechanism in which deregulated USP6 transcription results from juxtaposition to the highly active CDH11 promoter.
动脉瘤样骨囊肿（ABC）是一种具有局部侵袭性的骨病变，通常发生在生命的前二十年。ABC在历史上被认为是一种非肿瘤性病变，但最近的细胞遗传学数据显示，染色体带16q22和17p13存在克隆性重排，这表明至少部分ABC存在肿瘤性基础。在此我们表明，复发性ABC染色体易位t(16;17)(q22;p13)产生了一个融合基因，其中16q22上的成骨细胞钙黏蛋白11基因（CDH11）启动子区域与17p13上的整个泛素特异性蛋白酶USP6（Tre2）编码序列并列。CDH11-USP6融合转录本仅在具有t(16;17)的ABC中被证实，但其他ABC存在由其他细胞遗传学机制导致的CDH11或USP6重排。CDH11在骨中强烈表达，我们的研究结果提示了一种新的致癌机制，即USP6转录失调是由于与高活性CDH11启动子并列所致。
