A De Novo Mouse Model of C11orf95-RELA Fusion-Driven Ependymoma Identifies Driver Functions in Addition to NF-κB.

The majority of supratentorial ependymomas (ST-ependymomas) have few mutations but frequently display chromothripsis of chromosome 11q that generates a fusion between C11orf95 and RELA (RELAFUS). Neural stem cells transduced with RELAFUSex vivo form ependymomas when implanted in the brain. These tumors display enhanced NF-κB signaling, suggesting that this aberrant signal is the principal mechanism of oncogenesis. However, it is not known whether RELAFUS is sufficient to drive de novo ependymoma tumorigenesis in the brain and, if so, whether these tumors also arise from neural stem cells. We show that RELAFUS drives ST-ependymoma formation from periventricular neural stem cells in mice and that RELAFUS-induced tumorigenesis is likely dependent on a series of cell signaling pathways in addition to NF-κB

Growing Up Too Fast - Video

A 7 ½ year old boy presented in 2000 with precocious puberty (development of pubic hair, acne and rapid linear growth). Work-up included a brain MRI revealing a suprasellar mass, consistent with a visual pathway glioma. On ophthalmologic evaluation, he was noted to be 20/25 OU with a normal funduscopic exam. He was started on leuprorelin with improvement in his symptoms and followed with serial MRIs, showing slow increase in the size of the tumor. Two years after diagnosis, he was offered radiation therapy, but the family deferred treatment. Serial visual field testing showed a stable temporal defect in the right eye and mild nasal depression in the left eye, consistent with left optic tract involvement. He was lost to follow-up from August 2008 until June 2015 when he presented to the ER with 2 months of progressive right upper and lower extremity weakness. He denied any recent changes in his vision. Eye exam showed 20/20 acuity in both eyes, normal color vision, 2+ temporal pallor in both eyes and an incomplete right homonymous hemianopia on visual field testing. Repeat MRI showed a partially cystic and partially nodular enhancing mass, centered in the region of the left hypothalamus versus left optic tract, with associated infiltration of adjacent structures including the left thalamus and inferior left basal ganglia. A diagnostic procedure was performed

Growing Up Too Fast - Path PPT

A 7 ½ year old boy presented in 2000 with precocious puberty (development of pubic hair, acne and rapid linear growth). Work-up included a brain MRI revealing a suprasellar mass, consistent with a visual pathway glioma. On ophthalmologic evaluation, he was noted to be 20/25 OU with a normal funduscopic exam. He was started on leuprorelin with improvement in his symptoms and followed with serial MRIs, showing slow increase in the size of the tumor. Two years after diagnosis, he was offered radiation therapy, but the family deferred treatment. Serial visual field testing showed a stable temporal defect in the right eye and mild nasal depression in the left eye, consistent with left optic tract involvement. He was lost to follow-up from August 2008 until June 2015 when he presented to the ER with 2 months of progressive right upper and lower extremity weakness. He denied any recent changes in his vision. Eye exam showed 20/20 acuity in both eyes, normal color vision, 2+ temporal pallor in both eyes and an incomplete right homonymous hemianopia on visual field testing. Repeat MRI showed a partially cystic and partially nodular enhancing mass, centered in the region of the left hypothalamus versus left optic tract, with associated infiltration of adjacent structures including the left thalamus and inferior left basal ganglia. A diagnostic procedure was performed

Growing Up Too Fast - Abstract

A 7 ½ year old boy presented in 2000 with precocious puberty (development of pubic hair, acne and rapid linear growth). Work-up included a brain MRI revealing a suprasellar mass, consistent with a visual pathway glioma. On ophthalmologic evaluation, he was noted to be 20/25 OU with a normal funduscopic exam. He was started on leuprorelin with improvement in his symptoms and followed with serial MRIs, showing slow increase in the size of the tumor. Two years after diagnosis, he was offered radiation therapy, but the family deferred treatment. Serial visual field testing showed a stable temporal defect in the right eye and mild nasal depression in the left eye, consistent with left optic tract involvement. He was lost to follow-up from August 2008 until June 2015 when he presented to the ER with 2 months of progressive right upper and lower extremity weakness. He denied any recent changes in his vision. Eye exam showed 20/20 acuity in both eyes, normal color vision, 2+ temporal pallor in both eyes and an incomplete right homonymous hemianopia on visual field testing. Repeat MRI showed a partially cystic and partially nodular enhancing mass, centered in the region of the left hypothalamus versus left optic tract, with associated infiltration of adjacent structures including the left thalamus and inferior left basal ganglia. A diagnostic procedure was performed

Growing Up Too Fast - Presentation PPT

A 7 ½ year old boy presented in 2000 with precocious puberty (development of pubic hair, acne and rapid linear growth). Work-up included a brain MRI revealing a suprasellar mass, consistent with a visual pathway glioma. On ophthalmologic evaluation, he was noted to be 20/25 OU with a normal funduscopic exam. He was started on leuprorelin with improvement in his symptoms and followed with serial MRIs, showing slow increase in the size of the tumor. Two years after diagnosis, he was offered radiation therapy, but the family deferred treatment. Serial visual field testing showed a stable temporal defect in the right eye and mild nasal depression in the left eye, consistent with left optic tract involvement. He was lost to follow-up from August 2008 until June 2015 when he presented to the ER with 2 months of progressive right upper and lower extremity weakness. He denied any recent changes in his vision. Eye exam showed 20/20 acuity in both eyes, normal color vision, 2+ temporal pallor in both eyes and an incomplete right homonymous hemianopia on visual field testing. Repeat MRI showed a partially cystic and partially nodular enhancing mass, centered in the region of the left hypothalamus versus left optic tract, with associated infiltration of adjacent structures including the left thalamus and inferior left basal ganglia. A diagnostic procedure was performed

BRAF V600E-Mutated Ganglioglioma of the Optic Pathway: A Case Report and Review of the Literature

Gangliogliomas are slow growing, benign neoplasms of the central nervous system (CNS). These lesions are rare, accounting for 1.3% of all CNS tumors in adults (1) but are more common in children, representing up to 7.6% of pediatric CNS tumors

A De Novo Mouse Model of C11orf95-RELA Fusion-Driven Ependymoma Identifies Driver Functions in Addition to NF-κB

Summary: The majority of supratentorial ependymomas (ST-ependymomas) have few mutations but frequently display chromothripsis of chromosome 11q that generates a fusion between C11orf95 and RELA (RELAFUS). Neural stem cells transduced with RELAFUS ex vivo form ependymomas when implanted in the brain. These tumors display enhanced NF-κB signaling, suggesting that this aberrant signal is the principal mechanism of oncogenesis. However, it is not known whether RELAFUS is sufficient to drive de novo ependymoma tumorigenesis in the brain and, if so, whether these tumors also arise from neural stem cells. We show that RELAFUS drives ST-ependymoma formation from periventricular neural stem cells in mice and that RELAFUS-induced tumorigenesis is likely dependent on a series of cell signaling pathways in addition to NF-κB. : The C11orf95-RELA fusion (RELAFUS) has been found in a distinct subset of supratentorial ependymomas. Ozawa et al. show that RELAFUS is sufficient to drive ST-ependymoma formation from periventricular neural stem cells in mice. Furthermore, they show that RELAFUS-induced tumorigenesis might depend on other cell signaling pathways in addition to NF-κB. Keywords: ependymoma, fusion gene, NF-κB signaling, RCAS/tv-a system, mouse model, RELA, C11orf9