Subgroup-Specific Diagnostic, Prognostic, and Predictive Markers Influencing Pediatric Medulloblastoma Treatment.
Subgroup-Specific Diagnostic, Prognostic, and Predictive Markers Influencing Pediatric Medulloblastoma Treatment.
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DOI：
10.3390/diagnostics12010061
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发表时间：
2021-12-28
期刊：
影响因子：
--
通讯作者：
Mahapatra S
中科院分区：
文献类型：
--
作者：
Ray S;Chaturvedi NK;Bhakat KK;Rizzino A;Mahapatra S
髓母细胞瘤是小儿最常见的中枢神经系统恶性肿瘤。主要的治疗方法仍然是手术切除，然后进行颅脊髓放射和化疗，尽管这种治疗方法在最年轻的患者中有局限性。在临床上，肿瘤根据年龄、诊断时的转移情况和手术切除程度分为平均状态和高危状态。然而，高通量筛选的技术进步促进了对大型转录组数据集的分析，这些数据集已用于生成当前的分类系统，将患者分为四个主要亚组，即WNT（无翅），SHH（音刺猬）以及非SHH/WNT亚组3和4。每个亚组可以在细胞遗传学和表观遗传学事件的基础上进一步细分，其中一些在不同的信号通路中，激活影响患者预后的特定表型。在这里，我们通过回顾触发肿瘤转化或表现出致癌特性的关键基因的细胞遗传学事件的程度，深入研究每个亚群的遗传基础。这些讨论都进一步集中在如何利用这些遗传畸变为每个亚组产生新的靶向治疗方法，以及讨论目前在产生上述治疗方法中面临的挑战。我们未来的希望是，通过更好地了解亚群特异性细胞遗传学事件，该领域可以改善诊断、预后和治疗，以改善这些患者的整体生活质量。
Medulloblastoma (MB) is the most common malignant central nervous system tumor in pediatric patients. Mainstay of therapy remains surgical resection followed by craniospinal radiation and chemotherapy, although limitations to this therapy are applied in the youngest patients. Clinically, tumors are divided into average and high-risk status on the basis of age, metastasis at diagnosis, and extent of surgical resection. However, technological advances in high-throughput screening have facilitated the analysis of large transcriptomic datasets that have been used to generate the current classification system, dividing patients into four primary subgroups, i.e., WNT (wingless), SHH (sonic hedgehog), and the non-SHH/WNT subgroups 3 and 4. Each subgroup can further be subdivided on the basis of a combination of cytogenetic and epigenetic events, some in distinct signaling pathways, that activate specific phenotypes impacting patient prognosis. Here, we delve deeper into the genetic basis for each subgroup by reviewing the extent of cytogenetic events in key genes that trigger neoplastic transformation or that exhibit oncogenic properties. Each of these discussions is further centered on how these genetic aberrations can be exploited to generate novel targeted therapeutics for each subgroup along with a discussion on challenges that are currently faced in generating said therapies. Our future hope is that through better understanding of subgroup-specific cytogenetic events, the field may improve diagnosis, prognosis, and treatment to improve overall quality of life for these patients.
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影响因子：
16
作者：
Clarke TL;Sanchez-Bailon MP;Chiang K;Reynolds JJ;Herrero-Ruiz J;Bandeiras TM;Matias PM;Maslen SL;Skehel JM;Stewart GS;Davies CC
通讯作者：
Davies CC
影响因子：
5.7
作者：
Chaturvedi, Nagendra K.;Kling, Matthew J.;Coulter, Don W.
通讯作者：
Coulter, Don W.
影响因子：
11.5
作者：
Bobola, MS;Finn, LS;Silber, JR
通讯作者：
Silber, JR
影响因子：
8
作者：
Bolin, Sara;Borgenvik, Anna;Swartling, Fredrik J.
通讯作者：
Swartling, Fredrik J.
DOI：
10.1158/1078-0432.ccr-13-2281
发表时间：
2014-02-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Bandopadhayay P;Bergthold G;Nguyen B;Schubert S;Gholamin S;Tang Y;Bolin S;Schumacher SE;Zeid R;Masoud S;Yu F;Vue N;Gibson WJ;Paolella BR;Mitra SS;Cheshier SH;Qi J;Liu KW;Wechsler-Reya R;Weiss WA;Swartling FJ;Kieran MW;Bradner JE;Beroukhim R;Cho YJ
通讯作者：
Cho YJ