An Animal Model of MYC-Driven Medulloblastoma

Pei, Yanxin; Moore, Colin; Wang, Jun; Tewari, Alok K.; Eroshkin, Alexey; Cho, Yoon Jae; Witt, Hendrik; Korshunov, Andrey; Read, Tracy Ann; Sun, Julia; Schmitt, Earlene M.; Miller, C. Ryan; Buckley, Anne F.; McLendon, Roger E.; Westbrook, Thomas F.; Northcott, Paul A.; Taylor, Michael D.; Pfister, Stefan M.; Febbo, Phillip G.; Wechsler‐Reya, Robert J.

doi:10.1016/j.ccr.2011.12.021

Cited by 276 publications

(329 citation statements)

References 57 publications

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“…The resultant tumors showed that the LCA phenotypes were highly aggressive, and transcriptionally resembled group 3 MB. MYC withdrawal caused complete tumor regression (Pei et al 2012). These data suggest that MYC is a significant contributor to the initiation, maintenance, and progression of this disease (see Gabay et al 2013).…”

Section: Myc In the Group 3 Subgroupmentioning

confidence: 88%

“…However, because deprivation of MYC and MYCN in group 3 and group 4 models either induce senescence or apoptotic cell death (Swartling et al 2010;Pei et al 2012), several strategies are being considered to suppress MYC function either by regulating its expression or preventing its binding to partner proteins.…”

Section: Therapeutic Strategies For Medulloblastomamentioning

confidence: 99%

“…Our model was generated by enforced expression of the wild-type MYC gene in GNPs purified from Trp53-null mice (Kawauchi et al 2012); the other relied on enforced expression of a partially stabilized mutant of MYC (MYC T58A ) with a dominantnegative form of Trp53 in CD133/prominin 1-positive neural stem cells (NSCs) (Pei et al 2012). The resultant tumors showed that the LCA phenotypes were highly aggressive, and transcriptionally resembled group 3 MB.…”

Section: Myc In the Group 3 Subgroupmentioning

confidence: 99%

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Role of MYC in Medulloblastoma

Roussel

Robinson

2013

Cold Spring Harbor Perspectives in Medicine

134

109

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Since its discovery as an oncogene carried by the avian acute leukemia virus MC29 in myelocytomatosis (Roussel et al. 1979) and its cloning (Vennstrom et al. 1982), c-MYC (MYC), as well as its paralogs MYCN and MYCL1, has been shown to play essential roles in cycling progenitor cells born from proliferating zones during embryonic development, and in all proliferating cells after birth. MYC deletion induces cell-cycle exit or cell death, depending on the cell type and milieu, whereas MYC and MYCN amplification or overexpression promotes cell proliferation and occurs in many cancers. Here, we review the relationship of MYC family proteins to the four molecularly distinct medulloblastoma subgroups, discuss the possible roles MYC plays in each of these subgroups and in the developing cells of the posterior fossa, and speculate on possible therapeutic strategies targeting MYC.

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Section: Myc In the Group 3 Subgroupmentioning

confidence: 88%

Section: Therapeutic Strategies For Medulloblastomamentioning

confidence: 99%

Section: Myc In the Group 3 Subgroupmentioning

confidence: 99%

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Role of MYC in Medulloblastoma

Roussel

Robinson

2013

Cold Spring Harbor Perspectives in Medicine

134

109

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“…La mayoría muestra la histología clásica, aunque también en menor medida la variante de células grandes/anaplásica 16 . Los meduloblastomas de este grupo parecen originarse de los precursores neuronales de la capa granular externa de la región subventricular 22 .…”

Section: Subgrupos Molecularesunclassified

Meduloblastoma: de la clasificación histológica a la molecular

Pabón

Hoyos

Restrepo

et al. 2018

MedUPB

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RESUMENEl meduloblastoma es un tumor frecuente en la población pediátrica, pero es raro en pacientes adultos. Es la segunda causa de muerte por cáncer en menores de 15 años. El hallazgo de una lesión tumoral cerebelosa mediana o paramediana que capta el medio de contraste y que a menudo comprime el cuarto ventrículo sugiere la presencia de este tumor. A través del uso de estudios de expresión génica y marcadores moleculares se ha generado una nueva aproximación a la clasificación del meduloblastoma. Así, se ha venido a entender el concepto de meduloblastoma no como una patología sino como un grupo de patologías distintas clínica y molecularmente. La resonancia magnética nuclear espinal y la punción lumbar deben ser realizadas en todos los pacientes como parte de la evaluación de la extensión de la enfermedad, debido a que las leptomeninges espinales son un sitio frecuente de diseminación. El tratamiento implica idealmente la interacción de un grupo interdisciplinario que pueda ofrecer al paciente: cirugía, radioterapia y quimioterapia. El pronóstico depende de variables como edad (menor de tres años), diseminación de la enfermedad, residuo tumoral posquirúrgico, variante histológica de células grandes/anaplásico, y pertenecer al grupo 3 (grupo de amplificacón del MYC).Palabras clave: cerebelo; meduloblastoma; expresión génica; clasificación. ABSTRACTMedulloblastoma is a common tumor in children, but is rare in adults. It is the second most common cause of cancer-related death in patients under 15 years. The presence of a median or paramedian enhancing cerebellar mass, often compressing the fourth ventricle may indicate the presence of this tumor. Genetic and molecular markers offer a new approach to the understanding and classification of medulloblastomas. Hence, we have come to understand medulloblastoma not as a sole disease but rather, as a group of clinically and molecularly distinct pathologies. Magnetic resonance imaging of the spine and lumbar puncture must be performed in all patients as part of the assessment of the extent of disease, since spinal leptomeninges are common sites for metastatic dissemination. Ideally, its treatmeant involves an interdisciplinary group that provides surgery, radiotherapy, and chemotherapy. Prognosis depends upon variables such as age (under three years), metastatic dissemination, residual tumor after surgery, large cell/ anaplastic histological variant, and group 3 tumor (MYC amplification group).

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“…Les auteurs en concluent que les MB WNT sont issus de la transformation de progéniteurs neuronaux de la lèvre rhombique inférieure, dans lesquels s'opère une synergie entre mutations de CTNNB1 et TP53 qui induit l'oncogenèse. L'expression de la Cre recombinase dans ce modèle n'étant pas restreinte à la lèvre rhombique, cette hypothèse est encore controversée [8]. …”

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