Clonal selection drives genetic divergence of metastatic medulloblastoma.
Clonal selection drives genetic divergence of metastatic medulloblastoma.
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克隆选择驱动转移性髓母细胞瘤的遗传差异。
DOI：
10.1038/nature10825
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发表时间：
2012-02-15
期刊：
影响因子：
64.8
通讯作者：
Taylor, Michael D.
中科院分区：
文献类型：
--
作者：
Wu, Xiaochong;Northcott, Paul A.;Dubuc, Adrian;Dupuy, Adam J.;Shih, David J. H.;Witt, Hendrik;Croul, Sidney;Bouffet, Eric;Fults, Daniel W.;Eberhart, Charles G.;Garzia, Livia;Van Meter, Timothy;Zagzag, David;Jabado, Nada;Schwartzentruber, Jeremy;Majewski, Jacek;Scheetz, Todd E.;Pfister, Stefan M.;Korshunov, Andrey;Li, Xiao-Nan;Scherer, Stephen W.;Cho, Yoon-Jae;Akagi, Keiko;MacDonald, Tobey J.;Koster, Jan;McCabe, Martin G.;Sarver, Aaron L.;Collins, V. Peter;Weiss, William A.;Largaespada, David A.;Collier, Lara S.;Taylor, Michael D.
髓母细胞瘤是儿科最常见的恶性脑肿瘤，发生于小脑，通过软脑膜间隙的脑脊液扩散至大脑和脊髓。播散是预后不良的标志，在确诊时高达40%的儿童中发现，在大多数儿童复发时发现。因此，受影响的儿童将接受整个发育中的大脑和脊髓的放射治疗，然后进行大剂量化疗，从而对发育中的神经系统产生有害影响。对于髓母细胞瘤通过脑脊液扩散的机制研究较少，而髓母细胞瘤的转移在生物学上与原发肿瘤相似。在这里，我们展示了在小鼠和人类髓母细胞瘤中，个体的转移彼此极其相似，但与匹配的原发肿瘤不同。转移中的克隆性遗传事件可以在原发肿瘤的限制性亚克隆中得到证实，这表明只有原发肿瘤中的罕见细胞才有转移的能力。未能解释转移性髓母细胞瘤的两室性质可能是开发有效的靶向治疗的主要障碍。
Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord. Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and in most children at the time of recurrence. Affected children therefore are treated with radiation to the entire developing brain and spinal cord, followed by high-dose chemotherapy, with the ensuing deleterious effects on the developing nervous system. The mechanisms of dissemination through the cerebrospinal fluid are poorly studied, and medulloblastoma metastases have been assumed to be biologically similar to the primary tumour,. Here we show that in both mouse and human medulloblastoma, the metastases from an individual are extremely similar to each other but are divergent from the matched primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted subclone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of metastatic medulloblastoma could be a major barrier to the development of effective targeted therapies.
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影响因子：
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影响因子：
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