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。

　　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：

　　MorrissyAS,GarziaL,ShihDJ,ZuyderduynS,HuangX,etal.Divergentclonalselectiondominatesmedulloblastomaatrecurrence.Nature.2016Jan13.doi:10.1038/nature16478.

　　Aninternationalresearchteamfromdozensofresearchinstitutions,includingtheUnitedStatesandCanada,hasfoundevidencethatrecurrentcancerinmedulloblastomapatientsdoesnotnecessarilycomefromthesamesourceastheprimarytumor.Theresults,publishedinnaturerecently,describetheirgeneticworkusingmousemodelstosequencethewholegenomeofhumantumors,theirfindingsandwhatresearchersthinkneedstobedonetobettertreatpatients.

　　Theresearcherslearnedwhetherthetumorsformedaftersurgicalremovalofthefirsttumorweregeneticallyidenticaltotheprimarytumor.Becauseaftersurgery,thetreatmentmethodsarecustomizedbasedonthegeneticspectrumoftheprimarytumortoresistthegrowthofnewtumors,thisresearchisofgreatsignificance.Todothis,theresearchersusedtheSleepingBeautytransposonsystemtoinducemedulloblastomaformationintestmice.Theythentrackedthisbysimulatingthetypicalcourseoftreatmentprescribedtohumanpatientsabout60%ofhumanpatientshaverelapses.Theresearcherssequencedtissuesamplestakenfromprimaryandrecurrenttumors.

　　Thefinalsequencingresultsweresurprising,23identicalinsertionsiteswereidentifiedin11primarytumorsand40identicalinsertionsiteswereidentifiedinrecurrenttumors.However,theinsertionsitesbetweenprimarytumorsandrecurrenttumorswere"extremelydifferent".Theteamthensequencedtheentiregenomeofsmallscalehumanprimaryandrecurrenttumors.Theyreport"striking"geneticdifferencesbetweenprimaryandrecurrenttumors.Thissuggeststhattheprimarytumorandtherecurrenttumormaybecompletelydifferentclonesources.

　　Accordingtotheresearchers,therecurrenceofmedulloblastomaisnottheresultofprimarytumorregrowth,butthegrowthofanunrelateddaughtertumorthatisnottargetedbytreatment.Theysuggestthatfutureclinicaltrials,includingfurtherbiopsies,shouldpayattentiontotheidentificationofdaughtertumorstargetedbydifferenttherapies.

　　Aboutmedulloblastoma:

　　Medulloblastomaisamalignantgliomaoftheposteriorcranialfossainchildren,whichwasfirstnamedafterBaileyandCushing.Thecellmorphologyofmedulloblastomaissimilartothatofembryonicmedulloblastoma,sothisnameisused.Medulloblastisakindofprimitivenonpolarcell.Inhumanembryo,itisonlyseenintheposteriormedullaryvelum,whichisconsistentwiththefactthatmedulloblastomaismorecommonintheinferiorvermisofcerebellum.Medulloblastomaisthemostmalignantgliomainthebrain.

　　Medulloblastomaisafatalformofmalignanttumorthatformsneartheskullbaseofthebraindistinctfromotherbraintumors,whichtendtospreadtootherpartsofthebrainand/orspine.Theyareparticularlyaggressive,withahighrecurrencerateaftersurgery,andpainfullymanytimeschildrenarediagnosedwiththedisease.

　　Medulloblastomaisthemostmalignantgliomainthebrain.Itshighmalignancyismanifestedinthreeaspects:①extremelyrapidgrowth;②noteasytoremoveallthetumorcells;③thetumorcellstendtoproducedisseminatedimplantationalongthecerebrospinalfluid.Itmainlyoccursinchildrenundertheageof14,andrarelyinthoseovertheageof20.BothTorontoandPhiladelphiachildren&39;shospitalreportedthattheincidenceofmedulloblastomawassecondonlytocerebellarastrocytoma,andrankedsecondinchildren&39;sposteriorfossatumors.Inchildren,itaccountsfor10.7%ofgliomasand7.6%ofintracranialtumors.Intheliterature,itaccountsfor6.5%~10%ofgliomas.Theaverageageis14yearsold.Childrenunder12yearsoldaccountfor69%ofthetotalnumberofpatientswiththistumor.Thegenderratiois2:1.Inchildren,almostallofthemarelocatedinthevermisofcerebellum,protrudingintothefourthventricle,evenfillingthecisternofcerebellomedullary.Occasionallyseenincerebellarhemisphere.Inadults,medulloblastomaisoftenseenincerebellumandoccasionallyincerebralhemisphere,butsomescholarsthinkthatmedulloblastomadiagnosedasbrainisactuallyneuroblastoma.

　　Theaveragesurvivaltimewas0.9years.Theprognosisofadultswasbetterthanthatofchildren.Withthedevelopmentofclinicalmedicineandbasicresearchinrecentyears,theprognosisofpatientswithWilmstumorhasbeenimproved.Atpresent,mostofthe5yearsurvivalratesareover30%,andthehighestis80%.Individualcansurviveformorethantenyears.Questbelievesthattheimprovementofcurativeeffectisinseparablefromthepostoperativeattentiontoradiotherapyofthewholebrainandspinalcordaxis.Brucebelievesthatinrecentyears,therehasbeensignificantprogressinthetreatmentandresultsofmedulloblastomainchildren.Onlyoneofhis15newlyreportedcasesdied,andCTscanshowednosignoftumorrecurrence.Theprognosisofmedulloblastomaisrelatedtomanyfactors.Atpresent,thedegreeoftumorresectioniscloselyrelatedtotheprognosis.Totalresectioncansignificantlyimprovetheprognosis,Raimondibelievesthatthereisnosignificantdifferenceinsurvivalratebetweenpartialresectionandsimplebiopsy.

　　Postoperativeradiotherapyisanimportantmeanstoprolongthesurvivalperiod,andadjuvantchemotherapyalsoplaysarole.Inaddition,thereisacloserelationshipbetweenpatients&39;ageandprognosis.Mostoftheliteraturepointsoutthattheprognosisofolderchildrenandadultswithmedulloblastomaisbetter.Itshouldbenotedthattheprognosisofpatientswithrecurrenceandmetastasisismuchlowerthanthatofthefirsttreatment,evenifradiotherapyandchemotherapyareused,theywillnotgetsatisfactoryresults.

　　Inconclusion,therearemanyfactorsinfluencingtheprognosis.Thereisnodoubtthatthoroughresectionofthefocus,postoperativeradiotherapywithsufficientdose,andchemotherapyandothercomprehensivetreatmentmeasuresmaygreatlyprolongthesurvivalperiodandimprovethequalityoflifeofmedulloblastomapatients.

　　Originalsource:

　　MorrissyAS,GarziaL,ShihDJ,ZuyderduynS,Huang