来自美国，加拿大等数十个研究机构组成的一个国际研究小组发现的证据表明，在髓母细胞瘤（medulloblastoma）患者体内复发的癌症与原发肿瘤并不一定是同一来源。这项研究结果发表在近日的《自然》（Nature）杂志上，该研究描述了他们利用小鼠模型开展的遗传工作，对人类肿瘤进行的全基因组测序，他们的研究发现以及研究人员认为要更好地治疗患者需要去做的事情。胶质瘤资讯网指出，髓母细胞瘤是恶性脑瘤，患者应积极治疗来延长生命周期。

　　研究人员了解在手术切除首次发病的肿瘤后，形成的肿瘤在遗传上与原发肿瘤是否相同。由于在手术后都是基于原发肿瘤的遗传谱来量身定制设计治疗方法对抗新肿瘤生长，这一研究具有重要的意义。为此，研究人员利用了睡美人转座子系统在测试小鼠中诱导髓母细胞瘤形成。他们随后通过模拟给人类患者处方的典型治疗进程对此进行了追踪——大约60%的人类患者会出现肿瘤复发。研究人员从原发及复发肿瘤处采集组织样本后，进行了测序。

　　最终测序结果令人吃惊，在11个原发肿瘤中鉴别出了23个相同的插入位点，在复发肿瘤中鉴别出了40个相同的插入位点，然而，原发肿瘤与复发肿瘤之间的插入位点极其地不同。该研究小组随后对小规模的人类原发和复发肿瘤进行了全基因组测序。他们报告称在原发和复发肿瘤之间发现了惊人的遗传差异。这提示原发肿瘤与复发的肿瘤可能是完全不同的克隆来源。

　　研究人员由此认为，复发的髓母细胞瘤并非是原发肿瘤重新生长的结果，而是有可能由未被治疗靶向的一种不相关的子瘤生长而来。他们建议未来临床试验包括进一步的活组织检查应注意鉴别采用不同疗法靶向的子瘤。

　　关于髓母细胞瘤：

　　髓母细胞瘤(medulloblastoma)是首先由Bailey和Cushing命名的一种儿童后颅窝恶性胶质瘤。髓母细胞瘤的细胞形态很像胚胎期的髓母细胞，因此采用这个名称。髓母细胞是一种很原始的无极细胞。在人胚胎中仅见于后髓帆，这点与髓母细胞瘤好发于小脑下蚓部相符合。髓母细胞瘤是颅内恶性程度最高的胶质瘤。

　　髓母细胞瘤是在靠近颅底大脑部位形成的一种致命形式的恶性肿瘤——明显不同于其他的脑瘤，它们往往会扩散至大脑和/或脊柱的其他部位。它们尤其具有侵袭性，在手术切除后有着高复发率，令人心痛地是很多时候儿童被诊断出罹患此病。

　　髓母细胞瘤是颅内恶性程度最高的胶质瘤。其高度恶性表现在三个方面：①生长极其迅速；②手术不易全部切除；③肿瘤细胞有沿脑脊液产生播散性种植的倾向。主要发生于14岁以下的儿童，少数见于20岁以上者。多伦多和费城儿童医院皆报道髓母细胞瘤的发病率仅次于小脑星形细胞瘤而居儿童后颅窝肿瘤的第二位。在儿童占神经胶质瘤的10.7%，占颅内肿瘤7.6%。文献中占神经胶质瘤的6.5%~10%。平均年龄14岁，12岁以下的儿童占本肿瘤全数病人的69%，男女别比为2:1。在儿童几乎均位于小脑蚓部，突入第四脑室，甚至充满小脑延髓池。偶见于小脑半球。在成人亦多见于小脑，偶见于大脑半球，但有些学者认为诊断为大脑的髓母细胞瘤，实为神经母细胞瘤。

　　术后平均生存0.9年，成人的预后较儿童为好。随着近年来临床医学和基础研究的不断发展，随母细胞瘤病人的预后得到不断改善。目前多数统计5年存活率均在30%以上，最高统计达80%。个别的可生存达十年以上。Quest认为疗效的提高与术后重视对整个脑与脊髓轴进行放射治疗是分不开的。Bruce认为，最近几年来对儿童髓母细胞瘤的治疗与结果有明显的进步。他新报告的15例中仅1例死亡，且CT扫描证实无肿瘤复发的征象。髓母细胞瘤患者预后与多种因素有关。目前认为手术切除肿瘤的程度与预后密切相关。全切除可明显改善预后，Raimondi认为部分切除和单纯活检其生存率无明显差别。

　　术后放疗是延长生存期的重要手段，辅助化疗也有一定作用。此外患者年龄与预后也有密切关系，多数文献指出较大年龄的儿童及成人髓母细胞瘤患者的预后较好。应注意的是复发和有转移病例，其预后大大低于第一次治疗，即使使用放疗和化疗，也不会获得满意的疗效。

　　综上所述，影响预后的因素是多方面的。无疑，彻底切除病灶，术后辅以足够剂量的放疗，有条件配合化疗等综合治疗措施，可能会大大延长髓母细胞瘤患者的生存期和改善病人的生活质量。

　　原始出处：

　　Morrissy AS, Garzia L, Shih DJ, Zuyderduyn S, Huang X, et al.Divergent clonal selection dominates medulloblastoma at recurrence. Nature. 2016 Jan 13. doi: 10.1038/nature16478.

　　An international research team from dozens of research institutions, including the United States and Canada, has found evidence that recurrent cancer in medulloblastoma patients does not necessarily come from the same source as the primary tumor. The results, published in nature recently, describe their genetic work using mouse models to sequence the whole genome of human tumors, their findings and what researchers think needs to be done to better treat patients.

　　The researchers learned whether the tumors formed after surgical removal of the first tumor were genetically identical to the primary tumor. Because after surgery, the treatment methods are customized based on the genetic spectrum of the primary tumor to resist the growth of new tumors, this research is of great significance. To do this, the researchers used the Sleeping Beauty transposon system to induce medulloblastoma formation in test mice. They then tracked this by simulating the typical course of treatment prescribed to human patients - about 60% of human patients have relapses. The researchers sequenced tissue samples taken from primary and recurrent tumors.

　　The final sequencing results were surprising, 23 identical insertion sites were identified in 11 primary tumors and 40 identical insertion sites were identified in recurrent tumors. However, the insertion sites between primary tumors and recurrent tumors were "extremely different". The team then sequenced the entire genome of small-scale human primary and recurrent tumors. They report "striking" genetic differences between primary and recurrent tumors. This suggests that the primary tumor and the recurrent tumor may be completely different clone sources.

　　According to the researchers, the recurrence of medulloblastoma is not the result of primary tumor regrowth, but the growth of an unrelated daughter tumor that is not targeted by treatment. They suggest that future clinical trials, including further biopsies, should pay attention to the identification of daughter tumors targeted by different therapies.

　　About medulloblastoma:

　　Medulloblastoma is a malignant glioma of the posterior cranial fossa in children, which was first named after Bailey and Cushing. The cell morphology of medulloblastoma is similar to that of embryonic medulloblastoma, so this name is used. Medulloblast is a kind of primitive nonpolar cell. In human embryo, it is only seen in the posterior medullary velum, which is consistent with the fact that medulloblastoma is more common in the inferior vermis of cerebellum. Medulloblastoma is the most malignant glioma in the brain.

　　Medulloblastoma is a fatal form of malignant tumor that forms near the skull base of the brain - distinct from other brain tumors, which tend to spread to other parts of the brain and / or spine. They are particularly aggressive, with a high recurrence rate after surgery, and painfully many times children are diagnosed with the disease.

　　Medulloblastoma is the most malignant glioma in the brain. Its high malignancy is manifested in three aspects: ① extremely rapid growth; ② not easy to remove all the tumor cells; ③ the tumor cells tend to produce disseminated implantation along the cerebrospinal fluid. It mainly occurs in children under the age of 14, and rarely in those over the age of 20. Both Toronto and Philadelphia children's hospital reported that the incidence of medulloblastoma was second only to cerebellar astrocytoma, and ranked second in children's posterior fossa tumors. In children, it accounts for 10.7% of gliomas and 7.6% of intracranial tumors. In the literature, it accounts for 6.5% ~ 10% of gliomas. The average age is 14 years old. Children under 12 years old account for 69% of the total number of patients with this tumor. The gender ratio is 2:1. In children, almost all of them are located in the vermis of cerebellum, protruding into the fourth ventricle, even filling the cistern of cerebellomedullary. Occasionally seen in cerebellar hemisphere. In adults, medulloblastoma is often seen in cerebellum and occasionally in cerebral hemisphere, but some scholars think that medulloblastoma diagnosed as brain is actually neuroblastoma.

　　The average survival time was 0.9 years. The prognosis of adults was better than that of children. With the development of clinical medicine and basic research in recent years, the prognosis of patients with Wilms tumor has been improved. At present, most of the 5-year survival rates are over 30%, and the highest is 80%. Individual can survive for more than ten years. Quest believes that the improvement of curative effect is inseparable from the postoperative attention to radiotherapy of the whole brain and spinal cord axis. Bruce believes that in recent years, there has been significant progress in the treatment and results of medulloblastoma in children. Only one of his 15 newly reported cases died, and CT scan showed no sign of tumor recurrence. The prognosis of medulloblastoma is related to many factors. At present, the degree of tumor resection is closely related to the prognosis. Total resection can significantly improve the prognosis, Raimondi believes that there is no significant difference in survival rate between partial resection and simple biopsy.

　　Postoperative radiotherapy is an important means to prolong the survival period, and adjuvant chemotherapy also plays a role. In addition, there is a close relationship between patients' age and prognosis. Most of the literature points out that the prognosis of older children and adults with medulloblastoma is better. It should be noted that the prognosis of patients with recurrence and metastasis is much lower than that of the first treatment, even if radiotherapy and chemotherapy are used, they will not get satisfactory results.

　　In conclusion, there are many factors influencing the prognosis. There is no doubt that thorough resection of the focus, postoperative radiotherapy with sufficient dose, and chemotherapy and other comprehensive treatment measures may greatly prolong the survival period and improve the quality of life of medulloblastoma patients.

　　Original source:

　　Morrissy AS, Garzia L, Shih DJ, Zuyderduyn S, Huang