Subgroup-specific localization of human medulloblastoma based on pre-operative MRI

Wefers, Annika K.; Warmuth‐Metz, Monika; Pöschl, Julia; Bueren, André O. von; Monoranu, Camelia‐Maria; Seelos, Klaus; Peraud, Aurelia; Tonn, Jörg‐Christian; Koch, Arend; Pietsch, Torsten; Herold‐Mende, Christel; Mawrin, Christian; Meeteren, Antoinette Schouten-van; Vuurden, Dannis G. van; Hoff, Katja von; Rutkowski, Stefan; Pfister, Stefan M.; Kool, Marcel; Schüller, Ulrich

doi:10.1007/s00401-014-1271-5

Cited by 53 publications

(66 citation statements)

References 7 publications

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“…LCA, large cell/anaplastic; DNMB, desmoplastic/nodular medulloblastoma; SVZ, subventricular zone; NSC, neural stem cell; RT, radiotherapy. that WNT-MBs are almost always in contact with the brainstem and the fourth ventricle (27,28). Activation of Ctnnb1 in granule neuron precursors (GNPs) does not lead to tumorigenesis in mice; in contrast, Ctnnb1 activation in Blbp-expressing cells in the dorsal brainstem of mice interrupts cell migration and, in conjunction with deletion of Trp53, results in tumors that resemble human WNT-MB (26,29).…”

Section: Medulloblastomamentioning

confidence: 99%

“…G3-MB occurs more frequently in males than in females and includes a higher proportion of infants and young children than adults (8,9). Most G3 (and G4) MBs grow in the midline in proximity to the fourth ventricle or in contact with the brainstem (27,28); it is possible that this location facilitates access to cerebrospinal fluid and contributes to increased metastasis.…”

Section: Groupmentioning

confidence: 99%

“…Pediatric G4-MB patients have an intermediate survival rate, whereas adult patients often show a poor prognosis (11). Like G3-MB, G4-MBs are usually found adjacent to the fourth ventricle (27).…”

Section: Groupmentioning

confidence: 99%

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Molecular mechanisms and therapeutic targets in pediatric brain tumors

et al. 2017

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Brain tumors are among the leading causes of cancer-related deaths in children. Although surgery, aggressive radiation, and chemotherapy have improved outcomes, many patients still die of their disease. Moreover, those who survive often suffer devastating long-term side effects from the therapies. A greater understanding of the molecular underpinnings of these diseases will drive the development of new therapeutic approaches. Advances in genomics and epigenomics have provided unprecedented insight into the molecular diversity of these diseases and, in several cases, have revealed key genes and signaling pathways that drive tumor growth. These not only serve as potential therapeutic targets but also have facilitated the creation of animal models that faithfully recapitulate the human disease for preclinical studies. In this Review, we discuss recent progress in understanding the molecular basis of the three most common malignant pediatric brain tumors-medulloblastoma, ependymoma, and high-grade glioma-and the implications for development of safer and more effective therapies.

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Section: Medulloblastomamentioning

confidence: 99%

Section: Groupmentioning

confidence: 99%

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Molecular mechanisms and therapeutic targets in pediatric brain tumors

et al. 2017

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“…Some studies [19] classified medulloblastoma into three molecular subgroups (SHH, WNT, Non-SHH/WNT), instead of four subgroups (SHH, WNT, Group 3, and Group 4). There are two main reasons for the adoption of three subgroups: one is that Group 3 and Group 4 medulloblastoma were much less well defined and both showed neuronal/photoreceptor differentiation, and their clinical features were largely similar according to previous studies [10][11][12][18][19][20][21][22] . Another reason is the lack of reliable, rapid techniques to differentiate Group 3 and Group 4 [18] .…”

Section: Discussionmentioning

confidence: 80%

“…Signaling pathways or biological programs driving the pathogenesis of Group 3 and Group 4 subgroups have remained largely elusive [10] . Moreover, studies have demonstrated that these two subgroups overlap in both molecular profiling and clinical features [10][11][12][13] , and Group 3 and Group 4 subgroups together are called Non-SHH/WNT subgroup [14] . There is a controversy in the neurosurgical community that complete resection is prognostically superior to an incomplete resection.…”

Section: Introductionmentioning

confidence: 99%

Differences in the prognostic value of tumor extent of resection among the molecular subgroups of medulloblastoma:A single centre study of 113 cases

Wang

Xiong

et al. 2017

Transl. Neurosci. Clin.

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Immunohistochemistry and CTNNB1 exon 3 mutation analysis were used to determine the different subgroups. Complete or incomplete resection was defined based on surgeons' reports and confirmed by postoperative computer tomography (CT). In this study, we included 113 patients with medulloblastoma (13 with WNT subgroup, 18 with SHH subgroup, and 82 with non-SHH/WNT subgroups) to assess their event-free and overall survival. We identified event-free survival and overall survival benefit for complete resection over incomplete resection. We found that for patients with NON-SHH/WNT medulloblastoma, incomplete resection was significantly associated with progression and overall survival compared with complete resection. To our best knowledge, the present study is the first to demonstrate the prognostic value of tumor extent of resection among the molecular subgroups of 113 medulloblastoma in the Chinese population.The prognostic benefit of the increased extent of resection for patients with medulloblastoma is attenuated after the molecular subgroups are taken into account. We still need further study to assess the benefit of surgical resection of small residual portions.Citation Wang YY, Li KKW, Xiong J, Zhang ZY, Wang Y, Xu J, Wang Y, Ng HK, Zhong P. Differences in the prognostic value of tumor extent of resection among the molecular subgroups of medulloblastoma: A single centre study of 113 cases.

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