Central nervous system (CNS) tumors are the most common solid malignancy in the pediatric population. These lesions are the result of the aberrant cell signaling step proteins, which normally regulate cell proliferation. Mitogen-activated protein kinase (MAPK) pathways and tyrosine kinase receptors are involved in tumorigenesis of low-grade gliomas. High-grade gliomas may carry similar mutations, but loss of epigenetic control is the dominant molecular event; it can occur either due to histone mutations or inappropriate binding or unbinding of DNA on histones. Therefore, despite the absence of genetic alteration in the classic oncogenes or tumor suppressor genes, uncontrolled transcription results in tumorigenesis. Isocitric dehydrogenase (IDH) mutations do not predominate compared to their adult counterpart. Embryonic tumors include medulloblastomas, which bear mutations of transcription-regulating pathways, such as wingless-related integration sites or sonic hedgehog pathways. They may also relate to high expression ofMycfamily genes. Atypical teratoid rhabdoid tumors harbor alterations of molecules that contribute to ATP hydrolysis of chromatin. Embryonic tumors with multilayered rosettes are associated with microRNA mutations and impaired translation. Ependymomas exhibit great variability. As far as supratentorial lesions are concerned, the major events are mutations either of NFkB or Hippo pathways. Posterior fossa tumors are further divided into two types with different prognoses. Type A group is associated with mutations of DNA damage repair molecules. Lastly, germ cell tumors are a heterogeneous group. Among them, germinomas manifest KIT receptor mutations, a subgroup of the tyrosine kinase receptor family.
中枢神经系统肿瘤是儿童群体中最常见的实体恶性肿瘤。这些病变源于调控细胞增殖的信号通路蛋白异常。低级别胶质瘤的发生与丝裂原活化蛋白激酶通路及酪氨酸激酶受体密切相关。高级别胶质瘤可能携带类似突变，但表观遗传调控失常是其主要分子事件，可通过组蛋白突变或DNA与组蛋白异常结合/解离实现。因此，即使经典癌基因或抑癌基因未发生遗传学改变，失控的转录过程仍可导致肿瘤发生。与成人患者相比，异柠檬酸脱氢酶突变在此类肿瘤中不占主导地位。 胚胎性肿瘤包括髓母细胞瘤，其特征为转录调控通路（如Wnt或Shh通路）突变，也可能与Myc家族基因高表达相关。非典型畸胎样/横纹肌样肿瘤存在影响染色质ATP水解功能的分子改变。多层菊形团胚胎性肿瘤则与微小RNA突变及翻译过程受损有关。 室管膜瘤具有高度异质性。幕上病变主要涉及NFκB或Hippo通路突变。后颅窝肿瘤根据预后差异可分为两类：A型与DNA损伤修复分子突变相关。最后，生殖细胞肿瘤构成异质性群体，其中生殖细胞瘤以酪氨酸激酶受体家族中的KIT受体突变为特征。
The Molecular Basis of Pediatric Brain Tumors: A Review with Clinical Implications
肿瘤(癌症)患者之家