Hedgehog checkpoints in medulloblastoma: the chromosome 17p deletion paradigm
Hedgehog checkpoints in medulloblastoma: the chromosome 17p deletion paradigm
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DOI：
10.1016/j.molmed.2005.10.005
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发表时间：
2005-12-01
影响因子：
13.6
通讯作者：
Gulino, A
中科院分区：
文献类型：
--
作者：
Ferretti, E;De Smaele, E;Gulino, A
髓母细胞瘤经常不适当地激活Hedgehog信号。这一发现表明，仅在少数肿瘤中存在这一途径组成部分的突变，这表明额外的遗传或表观遗传损伤也可能导致Hedgehog失调。染色体17p缺失是髓母细胞瘤中最常见的遗传损伤，最近被认为是Hedgehog信号失控的原因。这种缺失导致一种新的Hedgehog拮抗剂RENKCTD11的丢失，从而消除了小脑发育和肿瘤发生过程中Hedgehog依赖事件的检查点。映射到17P的额外Hedgehog调节剂的破坏表明了旨在阻断Hedgehog途径的合作激活的多靶点治疗策略的基础。
Medulloblastomas often activate Hedgehog signaling inappropriately. The finding that mutations in components of this pathway are present only in few tumors suggests that additional genetic or epigenetic lesions can also lead to Hedgehog dysregulation. Chromosome 17p deletion, the most frequently detected genetic lesion in medulloblastoma, has recently been identified as a cause of unrestrained Hedgehog signaling. Such a deletion leads to the loss of RENKCTD11, a novel Hedgehog antagonist, thus removing a checkpoint of Hedgehog-dependent events during cerebellum development and tumorigenesis. The disruption of additional Hedgehog modulators that map to 17p suggests a rationale for a multitargeted therapeutic strategy aimed at interrupting the cooperative activation of the Hedgehog pathway.