Frequent genomic abnormalities at TWIST in human pediatric osteosarcomas
Frequent genomic abnormalities at TWIST in human pediatric osteosarcomas
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DOI：
10.1002/ijc.21068
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发表时间：
2005-11-10
影响因子：
6.4
通讯作者：
Perrin-Schmitt, F
中科院分区：
文献类型：
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作者：
Entz-Werlé, N;Stoetzel, C;Perrin-Schmitt, F
识别特定肿瘤中染色体异常的标记基因可能有助于肿瘤发生机制的理解、癌症的检测、临床结果的预测和治疗反应。先前的生理学和肿瘤学数据证实twist基因是中胚层衍生物和骨组织分化的标志，但它在骨恶性肿瘤中的作用尚未被研究。在目前的研究中，对儿童高级别骨肉瘤基因组改变的搜索集中在7p21区域，更具体地说是TWIST基因。在74名患者的队列中，我们通过等位基因分型观察到，68个信息性肿瘤中有31个在扭转基因上重排。其中，定量聚合酶链式反应(QPCR)分析显示，令人惊讶的是，大多数人检测到了twist基因的缺失(22/68)，但也检测到了扩增(9/68)。此外，TWIST处的缺失与其他分子异常，如APC或c-KIT基因座的改变，以及临床特征，如不良预后，在统计上相关。这项工作表明，twist基因似乎与儿童高级别骨肉瘤有关，是一个可能具有初步预测价值的新标记。(C)2005年Wiley-Liss，Inc.
The identification of genes as markers for chromosome aberrations in specific tumors might facilitate oncogenesis mechanism comprehension, cancer detection, prediction of clinical outcomes, and response to therapy. Previous physiologic and oncologic data identified the TWIST gene as a marker for mesodermal derivative and bone tissue differentiation, but its contribution to bone malignancies has not been investigated. In the present study, search for genomic alterations in high-grade pediatric osteosarcomas was focused on the 7p21 region, and more specifically on the TWIST gene. In a cohort of 74 patients, we observed by allelotyping that 31 of 68 informative tumors were rearranged at the TWIST locus. Among them, analysis by quantitative PCR (QPCR) revealed that, surprisingly, mostly deletions (22/68), but also amplifications (9/68), of the TWIST gene were detected. Furthermore, deletions at TWIST were statistically correlated to other molecular abnormalities, like alterations at the APC or c-kit loci, as well as to clinical features such as a poor outcome. This work shows that the TWIST gene seemed to be involved in high-grade pediatric osteosarcomas and is a new marker with a possible initial predictive value. (c) 2005 Wiley-Liss, Inc.