小鼠脑毛细胞星型细胞瘤的组织切片图{图}
毛细胞星型细胞瘤是在儿童中最常见的脑肿瘤，通常生长缓慢且为良性。尽管如此，手术常常难于根除这种生长广泛的肿瘤。这意味着病人需要后续的治疗以去除剩余下来的肿瘤组织。化疗或放疗通常会导致明显的副作用且对这种缓慢生长的肿瘤疗效有限。因此，患病儿童急需一些新的，靶向性的疗法。
现在这种脑肿瘤的一个典型的基因缺失已经被发现。德国癌症研究中心的Peter Lichter教授说道：“从我们的研究中可以发现这种毛细胞星型细胞瘤在BRAF基因位上有缺失。”在正常细胞中仅仅在紧急情况下才启动的一条细胞信号通路，由于这个缺失而被永久性的激活。
海德尔堡大学的研究者们将包装有这种带有缺失的BRAF基因的病毒注射入小鼠的神经前导细胞中发现：有91%的小鼠在注射的部位有肿瘤的形成，且这种肿瘤的生物学特性、生长特性、组织结构和毛细胞星型细胞瘤类似。
这些肿瘤细胞还都具有一个缺失BRAF基因的典型特征：具有永久激活的MAP激酶活性。说明这一个基因的缺失的确足够引起毛细胞星型细胞瘤的产生。
Lichter教授说：“现在，我们可以为毛细胞星型细胞瘤建立一个有效的动物模型，以方便我们测试不同的新型酶抑制剂或新药物，使得更为有效的治疗这种疾病。”
生物探索推荐：
Nature：肿瘤细胞周期调控的一种关键因子——CUEDC2
Nature Materials：“侦察”肿瘤的纳米粒子被研制出
生物探索推荐英文摘要：
An activated mutant BRAF kinase domain is sufficient to induce pilocytic astrocytoma in mice.
Pilocytic astrocytoma (PA) is the most common type of primary brain tumor in children and the second most frequent cancer in childhood. Children with incompletely resected PA represent a clinically challenging patient cohort for whom conventional adjuvant therapies are only moderately effective. This has produced high clinical demand for testing of new molecularly targeted treatments. However, the development of new therapeutics for PA has been hampered by the lack of an adequate in vivo tumor model. Recent studies have identified activation of MAPK signaling, mainly by oncogenic BRAF activation, as a hallmark genetic event in the pathogenesis of human PA. Using in vivo retroviral somatic gene transfer into mouse neural progenitor cells, we have shown here that ectopic expression of the activated BRAF kinase domain is sufficient to induce PA in mice. Further in vitro analyses demonstrated that overexpression of activated BRAF led to increased proliferation of primary mouse astrocytes that could be inhibited by treatment with the kinase inhibitor sorafenib. Our in vivo model for PA shows that the activatedBRAF kinase domain is sufficient to induce PA and highlights its role as a potential therapeutic target.
