Advances in Genomics Explain Medulloblastoma Behavior at the Bedside
Advances in Genomics Explain Medulloblastoma Behavior at the Bedside
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DOI：
10.1093/neuros/nyx248
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发表时间：
2017-09-01
期刊：
影响因子：
4.8
通讯作者：
Taylor, Michael D.
中科院分区：
文献类型：
--
作者：
Kuzan-Fischer, ClaudiaM;Stucklin, Ana S. Guerreiro;Taylor, Michael D.
中枢神经系统（CNS）肿瘤是最常见的儿科实体瘤，也是儿童和青少年癌症相关死亡的主要原因。髓母细胞瘤（MB）是临床上侵袭性的，快速生长的胚胎性肿瘤，由于小脑发育异常而发生在后颅窝。1，2它们占所有儿童恶性CNS肿瘤的20%左右。3-5自从Bailey和库欣首次提出“髓母细胞瘤”一词来描述小脑的所有小圆形蓝细胞肿瘤以来，我们对这些肿瘤的理解有了很大的发展。在20世纪90年代，在非典型畸胎样/横纹肌样肿瘤（ATRT）中发现肿瘤抑制基因hSNF 5/INI 1的改变，使病理学家首次将MB与ATRT区分开来。7，8随后的基因组研究的爆炸进一步导致了不同MB分子亚群的鉴定-无翼（WNT），Sonic hedgehog（SHH），第3组和第4组-以及分子分析技术的进步为基于生物学的患者风险分层奠定了基础，并为探索靶向特定分子改变的新一代临床试验奠定了基础。9-13 MB患者的当前治疗包括手术切除、颅脊髓照射（用于3岁以上的儿童）和化疗，化疗确实治愈了大多数诊断为MB的患者。14，15然而，这些强化治疗与显著的长期毒性相关，例如，神经认知缺陷、神经内分泌功能缺陷、耳聋、生育力下降和辐射诱导的癌症。此外，转移性疾病对常规治疗反应较差，缩写：ATRT，非典型畸胎瘤样/横纹肌样肿瘤; CNS，中枢神经系统; MB，髓母细胞瘤; PARP，聚（ADP-核糖）聚合酶;
Central nervous system (CNS) tumors are the most prevalent pediatric solid tumors and a major cause of cancer-related mortality in children and adolescents. Medulloblastomas (MBs) are clinically aggressive, fastgrowing embryonal tumors that arise in the posterior fossa due to aberrations of cerebellar development. 1, 2 They make up about 20% of all malignant childhood CNS tumors. 3-5 Since Bailey and Cushing first introduced the term “medulloblastoma” to describe all small round blue cell tumors of the cerebellum, 6 our understanding of these tumors has greatly evolved. During the 1990s, the discovery of alterations in the tumor suppressor gene hSNF5/INI1 in atypical teratoid/rhabdoid tumors (ATRT) allowed pathologists to distinguish MBs from ATRTs for the first time. 7, 8 The explosion of genomic studies that followed further led to the identification of distinct MB molecular subgroups—Wingless (WNT), Sonic hedgehog (SHH), group 3, and group 4—and advances in molecular profiling techniques set the stage for biology-based risk stratification of patients, and a new generation of clinical trials that explore targeting specific molecular alterations. 9-13 Current therapy for MB patients includes surgical resection, craniospinal irradiation (for children older than 3 yr of age), and chemotherapy, which does cure the majority of patients diagnosed with MB. 14, 15 However, these intensive therapies are associated with significant long-term toxicities, eg, neurocognitive deficits, deficits in neuroendocrine functions, deafness, diminished fertility, and radiation induced cancers. 4, 16 Furthermore, metastatic disease responds poorly to conventional therapy, andABBREVIATIONS: ATRT, atypical teratoid/rhabdoid tumors; CNS, central nervous system; MB, medulloblastoma; PARP, poly (ADP-ribose) polymerase;