Alterations of the p53 and PIK3CA/AKT/mTOR pathways in angiosarcomas: a pattern distinct from other sarcomas with complex genomics.
Alterations of the p53 and PIK3CA/AKT/mTOR pathways in angiosarcomas: a pattern distinct from other sarcomas with complex genomics.
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DOI：
10.1002/cncr.27614
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发表时间：
2012-12-01
期刊：
影响因子：
6.2
通讯作者：
Antonescu, Cristina R.
中科院分区：
文献类型：
--
作者：
Italiano, Antoine;Chen, Chun-Liang;Thomas, Rachael;Breen, Matthew;Bonnet, Francoise;Sevenet, Nicolas;Longy, Michel;Maki, Robert G.;Coindre, Jean-Michel;Antonescu, Cristina R.
关键词：
p53和PIK 3CA/AKT/mTOR通路在具有复杂基因组的肉瘤中经常改变，例如平滑肌肉瘤（LMS）或未分化多形性肉瘤（UPS）。在血管肉瘤中，这些通路的遗传异常程度仍不清楚。我们研究了一系列62例AS中参与p53和PIK 3CA/AKT/mTOR通路的关键基因的状态。TP 53基因突变率为4%，缺失率为0。免疫组化检测到49%的p53过表达，与较差的无病生存率相关。虽然p14失活或HDM 2过表达在LMS和UPS中很常见，并可替代TP 53突变或缺失，但这种改变在血管瘤中很少见。在42%的病例中观察到pS 6 K和/或p-4 eBP 1过表达，表明血管瘤中PIK 3CA/AKT/mTOR通路的频繁激活。激活与PTEN基因内缺失无关，PTEN基因内缺失是LMS和UPS中常见的畸变，但在血管瘤中不存在。血管瘤是肉瘤中一个独特的亚群，具有复杂的基因组学。虽然TP 53突变和PTEN缺失在LMS和UPS中很常见，但这些异常很少参与AS的发病。
The p53 and the PIK3CA/AKT/mTOR pathways are frequently altered in sarcoma with complex genomics such as leiomyosarcoma (LMS) or undifferentiated pleomorphic sarcoma (UPS). The scale of genetic abnormalities in these pathways remains unknown in angiosarcoma. We investigated the status of critical genes involved in the p53 and the PIK3CA/AKT/mTOR pathways in a series of 62 AS. The mutation and deletion rates of TP53 were 4% and 0, respectively. p53 overexpression was detected by immunohistochemistry in 49% of cases and was associated with inferior disease-free survival. Although p14 inactivation or HDM2 overexpression are frequent in LMS and UPS and could substitute for TP53 mutation or deletion, such alterations were rare in angiosarcomas. pS6K and/or p-4eBP1 overexpression was observed in 42% of cases suggesting frequent activation of the PIK3CA/AKT/mTOR pathway in angiosarcomas. Activation was not related to intragenic deletion of PTEN, an aberration that is frequent in LMS and UPS, but absent in angiosarcomas. Angiosarcomas constitute a distinct subgroup among sarcomas with complex genomics. Although TP53 mutation and PTEN deletion are frequent in LMS and UPS, these aberrations are rarely involved in the pathogenesis of AS.
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影响因子：
3.7
作者：
Guo, Tianhua;Zhang, Lei;Chang, Ning-En;Singer, Samuel;Maki, Robert G.;Antonescu, Cristina R.
通讯作者：
Antonescu, Cristina R.
DOI：
10.1073/pnas.95.25.14950
发表时间：
1998-12-08
影响因子：
11.1
作者：
Aoki, M;Batista, O;Vogt, PK
通讯作者：
Vogt, PK
DOI：
10.1097/pdm.0b013e31815d0588
发表时间：
2008-09-01
期刊：
Diagnostic molecular pathology : the American journal of surgical pathology, part B
影响因子：
--
作者：
Baohua, Yu;Xiaoyan, Zhou;Daren, Shi
通讯作者：
Daren, Shi
影响因子：
4.7
作者：
HOLLSTEIN, M;MARION, MJ;MONTESANO, R
通讯作者：
MONTESANO, R
影响因子：
82.9
作者：
Hernando, Eva;Charytonowicz, Elizabeth;Cordon-Cardo, Carlos
通讯作者：
Cordon-Cardo, Carlos