Consistent MYC and FLT4 gene amplification in radiation-induced angiosarcoma but not in other radiation-associated atypical vascular lesions.
Consistent MYC and FLT4 gene amplification in radiation-induced angiosarcoma but not in other radiation-associated atypical vascular lesions.
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DOI：
10.1002/gcc.20827
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发表时间：
2011-01
影响因子：
3.7
通讯作者：
Antonescu, Cristina R.
中科院分区：
文献类型：
--
作者：
Guo, Tianhua;Zhang, Lei;Chang, Ning-En;Singer, Samuel;Maki, Robert G.;Antonescu, Cristina R.
血管肉瘤（AS）是一组独特的肉瘤，其特征是血管特异性受体酪氨酸激酶（包括TIE 1、KDR、TEK和FLT 1）上调。与临床异质性保持一致，基因表达谱区分两个AS基因组簇，其与解剖位置和先前暴露于辐射相关。此外，由于MYC扩增，高百分比的继发性AS而不是原发性AS显示出明显的8q24染色体增益。在这项研究中，我们挖掘了10种继发性AS和11种原发性AS的转录输出，以更好地定义这两个临床子集发病机制的二分法。MYC的致癌作用在继发性AS，以及放射诱导的非典型血管病变（AVL）和其他放射相关肉瘤中进行了进一步研究。在100%的继发性AS中发现了高水平的MYC扩增，但在AVL或其他放射相关肉瘤中没有发现。在25%的继发性AS中发现了FLT4（编码VEGFR3）的共扩增，但在其他类型中未发现。我们的研究结果加强了AS亚型的独特发病机制，MYC扩增是继发性AS的早期但必要的事件。次级遗传命中，如FLT4基因共扩增或KDR突变，可能在肿瘤进展中发挥作用，以及潜在的治疗靶向。
Angiosarcoma (AS) is a distinct group of sarcomas characterized by up-regulation of vascular-specific receptor tyrosine kinases, including TIE1, KDR, TEK, and FLT1. In keeping with the clinical heterogeneity, gene expression profiling distinguishes two AS genomic clusters, which correlate with anatomic location and prior exposure to radiation. Furthermore, a high percentage of secondary AS, but not primary AS, show distinct 8q24 chromosomal gains, due to MYC amplification. In this study we mined the transcriptional output of 10 secondary and 11 primary AS to better define the dichotomy in the pathogenesis of these two clinical subsets. The oncogenic role of MYC was investigated further in secondary AS, as well as in radiation-induced atypical vascular lesions (AVL) and other radiation-associated sarcomas. High level MYC amplification was found in 100% of secondary AS, but in none of the AVL or other radiation-associated sarcomas. Co-amplification of FLT4 (encoding VEGFR3) was identified in 25% of secondary AS, but not in other types. Our findings reinforce the distinct pathogenesis of AS subtypes, with MYC amplification being an early, but necessary event in secondary AS. Secondary genetic hits, such as FLT4 gene co-amplification or KDR mutations, may play a role in tumor progression, as well as potential therapeutic targeting.
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影响因子：
64.8
作者：
KRETZNER, L;BLACKWOOD, EM;EISENMAN, RN
通讯作者：
EISENMAN, RN
影响因子：
2.6
作者：
Sheppard, DG;Libshitz, HI
通讯作者：
Libshitz, HI
DOI：
10.1073/pnas.1434429100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Chi, JT;Chang, HY;Brown, PO
通讯作者：
Brown, PO
DOI：
10.1073/pnas.79.24.7837
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
TAUB, R;KIRSCH, I;LEDER, P
通讯作者：
LEDER, P
影响因子：
5.3
作者：
Spotts, GD;Patel, SV;Hann, SR
通讯作者：
Hann, SR