Downregulation of NDUFB6 due to 9p24.1-p13.3 loss is implicated in metastatic clear cell renal cell carcinoma.
Downregulation of NDUFB6 due to 9p24.1-p13.3 loss is implicated in metastatic clear cell renal cell carcinoma.
复制标题
由于9p24.1-P13.3损失引起的NDUFB6的下调与转移性透明细胞肾细胞癌有关。
DOI：
10.1002/cam4.351
复制
发表时间：
2015-01
期刊：
影响因子：
4
通讯作者：
Moriyama, Masatsugu
中科院分区：
文献类型：
--
作者：
Narimatsu, Takahiro;Matsuura, Keiko;Nakada, Chisato;Tsukamoto, Yoshiyuki;Hijiya, Naoki;Kai, Tomoki;Inoue, Toru;Uchida, Tomohisa;Nomura, Takeo;Sato, Fuminori;Seto, Masao;Takeuchi, Ichiro;Mimata, Hiromitsu;Moriyama, Masatsugu
本研究旨在阐明转移性透明细胞肾细胞癌（ccRCC）的基因组谱，并确定导致转移发展的基因。我们使用基于阵列的比较基因组杂交分析了20例原发性ccRCC及其相应转移瘤的基因组图谱，并确定了32个染色体区域，其中转移瘤中检测到的基因拷贝数改变比原发性肿瘤更频繁。在这32个区域中，9p24.1-p13.3丢失是统计学上最显著的改变。此外，我们发现原发性肿瘤中9p24.1-p13.3缺失的患者表现出显著较低的无复发率和癌症特异性生存率，这表明原发性肿瘤中9 p缺失是预测转移早期复发的潜在生物标志物。有趣的是，具有9 p丢失的原发性肿瘤的基因组谱与其相应的转移瘤的基因组谱相似，尽管9 p丢失在来自没有9 p丢失的原发性肿瘤的转移瘤中积累。mRNA表达水平的比较显示，位于9p24.1-p13.3的58个基因中的2个由于ccRCC中的基因拷贝数丢失而下调。在ccRCC细胞系中这两个基因的过表达研究揭示，由于9p24.1-p13.3处的缺失导致的NDUFB 6的下调可能赋予转移性ccRCC细胞生长优势。这些结果通过分析从癌症基因组图谱（TCGA）获得的405例ccRCC病例的数据得到证实。基于我们目前的数据，我们提出NDUFB 6是转移性ccRCC的可能的肿瘤抑制因子。
This study was conducted to clarify the genomic profiles of metastatic clear cell renal cell carcinomas (ccRCCs) and identify the genes responsible for development of metastasis. We analyzed the genomic profiles of 20 cases of primary ccRCC and their corresponding metastases using array-based comparative genomic hybridization, and identified 32 chromosomal regions in which gene copy number alterations were detected more frequently in metastases than in the primary tumors. Among these 32 regions, 9p24.1-p13.3 loss was the most statistically significant alteration. Furthermore, we found that patients with 9p24.1-p13.3 loss in primary tumors exhibited significantly lower rates of recurrence-free and cancer-specific survival, suggesting that 9p loss in the primary tumor is a potential biomarker predicting early recurrence of metastasis. Interestingly, the genomic profiles of primary tumors with 9p loss resembled those of their corresponding metastases, though 9p loss was accumulated in the metastases derived from the primary tumors without 9p loss. Comparison of the mRNA expression levels revealed that 2 of 58 genes located at 9p24.1-p13.3 were downregulated due to gene copy number loss in ccRCCs. An overexpression study of these two genes in ccRCC cell lines revealed that downregulation of NDUFB6 due to loss at 9p24.1-p13.3 may confer a growth advantage on metastatic ccRCC cells. These results were confirmed by analyzing the data of 405 cases of ccRCC obtained from The Cancer Genome Atlas (TCGA). On the basis of our present data, we propose that NDUFB6 is a possible tumor suppressor of metastatic ccRCCs.
登录
查看更多内容
影响因子：
21.3
作者：
Vincent, Theresa;Neve, Etienne P. A.;Johnson, Jill R.;Kukalev, Alexander;Rojo, Federico;Albanell, Joan;Pietras, Kristian;Virtanen, Ismo;Philipson, Lennart;Leopold, Philip L.;Crystal, Ronald G.;Garcia de Herreros, Antonio;Moustakas, Aristidis;Pettersson, Ralf F.;Fuxe, Jonas
通讯作者：
Fuxe, Jonas
DOI：
10.1158/1078-0432.ccr-09-2131
发表时间：
2009-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Young AC;Craven RA;Cohen D;Taylor C;Booth C;Harnden P;Cairns DA;Astuti D;Gregory W;Maher ER;Knowles MA;Joyce A;Selby PJ;Banks RE
通讯作者：
Banks RE
DOI：
10.1016/j.bbrc.2011.09.078
发表时间：
2011-10-22
影响因子：
3.1
作者：
Loublier, Sandrine;Bayot, Aurelien;Rustin, Pierre
通讯作者：
Rustin, Pierre
影响因子：
56.9
作者：
Ishikawa, Kaori;Takenaga, Keizo;Hayashi, Jun-Ichi
通讯作者：
Hayashi, Jun-Ichi
影响因子：
7.5
作者：
Brunelli, Matteo;Eccher, Albino;Martignoni, Guido
通讯作者：
Martignoni, Guido