Genotranscriptomic meta-analysis of the Polycomb gene CBX2 in human cancers: initial evidence of an oncogenic role.
Genotranscriptomic meta-analysis of the Polycomb gene CBX2 in human cancers: initial evidence of an oncogenic role.
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DOI：
10.1038/bjc.2014.474
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发表时间：
2014-10-14
影响因子：
8.8
通讯作者：
Helgason, C. D.
中科院分区：
文献类型：
--
作者：
Clermont, P-L;Sun, L.;Crea, F.;Thu, K. L.;Zhang, A.;Parolia, A.;Lam, W. L.;Helgason, C. D.
Polycomb group（PcG）蛋白是已知在多种人类癌症中使关键肿瘤抑制基因转录沉默的组蛋白修饰剂。染色体盒蛋白（CBX 2、4、6、7和8）是PcG介导的阻遏的关键组分。其中四个与肿瘤生物学有关，但CBX 2在癌症中的作用在很大程度上尚未确定。为了解决这个问题，我们使用COSMIC和Oncomine数据库对CBX 2在人类癌症中进行了全面和无偏见的基因转录组荟萃分析。我们发现了基因表达的变化，这表明CBX 2具有广泛的致癌作用。我们对29种组织类型的8013例肿瘤进行了遗传分析，结果显示没有失活染色体畸变，CBX 2基因座仅有40个点突变。相比之下，CBX 2扩增的总体速率在所有组合肿瘤中平均为10%，但在卵巢、乳腺和肺肿瘤中超过30%。此外，转录组学分析显示，与正常组织相比，在许多癌症中CBX 2 mRNA水平增加的强烈趋势，独立于CDKN 2 A/B沉默。此外，CBX 2上调和扩增与许多癌症类型（特别是乳腺癌）的转移进展和较低的总生存率显著相关。总体而言，我们报告CBX 2的分子特征提示了致癌作用。由于CBX 2从未在人类肿瘤中进行过研究，因此我们的结果为进一步研究CBX 2在癌细胞中的功能提供了理论基础。
Polycomb group (PcG) proteins are histone modifiers known to transcriptionally silence key tumour suppressor genes in multiple human cancers. The chromobox proteins (CBX2, 4, 6, 7, and 8) are critical components of PcG-mediated repression. Four of them have been associated with tumour biology, but the role of CBX2 in cancer remains largely uncharacterised. Addressing this issue, we conducted a comprehensive and unbiased genotranscriptomic meta-analysis of CBX2 in human cancers using the COSMIC and Oncomine databases. We discovered changes in gene expression that are suggestive of a widespread oncogenic role for CBX2. Our genetic analysis of 8013 tumours spanning 29 tissue types revealed no inactivating chromosomal aberrations and only 40 point mutations at the CBX2 locus. In contrast, the overall rate of CBX2 amplification averaged 10% in all combined neoplasms but exceeded 30% in ovarian, breast, and lung tumours. In addition, transcriptomic analyses revealed a strong tendency for increased CBX2 mRNA levels in many cancers compared with normal tissues, independently of CDKN2A/B silencing. Furthermore, CBX2 upregulation and amplification significantly correlated with metastatic progression and lower overall survival in many cancer types, particularly those of the breast. Overall, we report that the molecular profile of CBX2 is suggestive of an oncogenic role. As CBX2 has never been studied in human neoplasms, our results provide the rationale to further investigate the function of CBX2 in the context of cancer cells.
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影响因子：
3.7
作者：
Agherbi H;Gaussmann-Wenger A;Verthuy C;Chasson L;Serrano M;Djabali M
通讯作者：
Djabali M
影响因子：
11.2
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Walsh MJ
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50.3
作者：
Gargiulo, Gaetano;Cesaroni, Matteo;van Lohuizen, Maarten
通讯作者：
van Lohuizen, Maarten
影响因子：
56.9
作者：
Cao, R;Wang, LJ;Zhang, Y
通讯作者：
Zhang, Y
影响因子：
4.3
作者：
Forzati, Floriana;Federico, Antonella;Fusco, Alfredo
通讯作者：
Fusco, Alfredo