Faculty Bibliography
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288
Divergent clonal selection dominates medulloblastoma at recurrence
The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.
PMCID:4936195
PMID: 26760213
ISSN: 1476-4687
CID: 1912632
BRAF alteration status and the histone H3F3A gene K27M mutation segregate spinal cord astrocytoma histology
PMCID:4698284
PMID: 26487540
ISSN: 1432-0533
CID: 1810512
ACTA NEUROPATHOLOGICA COMMUNICATIONS [Letter]
ISI:000381339100002
ISSN: 2051-5960
CID: 5883592
Endoscopic resection of solid intraventricular tumors in children [Meeting Abstract]
Objective: We report the feasibility and outcomes of endoscopic resection of select intraventricular tumors in children. Methods: The clinical characteristics of 11 children with solid intraventricular tumors who underwent tumor resection were reviewed. 12 procedures were performed. Results: Gross total resection was achieved in 11 of 12 cases (92%). Maximal diameter ranged from 9-26 mm (mean 16.6 mm). Pathology included subependymal giant cell astrocytomas (SEGA), ependymomas, non-germinomatous germ cell tumor (NGGCT) and pilocytic astrocytoma. Mean follow-up was 35 months (range 10-109 months). All patients returned to their neurological baseline following surgery. Local tumor recurrence occurred in one patient and distant recurrence in another. Complications occurred in one patient, no permanent morbidity or mortality occurred. Hydrocephalus was present preoperatively in 5 cases and was treated with tumor removal alone or with additional endoscopic third ventriculostomy. No patient required a ventriculoperitoneal shunt. Conclusion: Neuroendoscopic gross-total resection of solid intraventricular tumors is a safe procedure in carefully selected pediatric patients
EMBASE:72187571
ISSN: 0256-7040
CID: 1950582
NOVEL CANDIDATE ONCOGENIC DRIVERS IN PINEOBLASTOMA [Meeting Abstract]
ISI:000361304800094
ISSN: 1523-5866
CID: 2687502
EFFECTS OF EVEROLIMUS ON MENINGIOMA GROWTH IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2 [Meeting Abstract]
ISI:000361304800159
ISSN: 1522-8517
CID: 2964282
Novel Candidate Oncogenic Drivers in Pineoblastoma [Meeting Abstract]
ISI:000354824800135
ISSN: 0022-3069
CID: 1620172
Biopsy-Proven Spontaneous Regression of a Rhabdomyomatous Mesenchymal Hamartoma
Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare, benign, congenital tumor of the dermis and subcutaneous tissue comprised of skeletal muscle and adipose and adnexal elements. Although the majority of cases are an incidental finding in otherwise healthy patients, some have been reported in association with other anomalies. We present a full-term boy evaluated on day 2 of life for two lesions located on the midline of the lower back and right buttock that each appeared clinically as an atrophic, pink plaque. Ultrasound of the midline lesion revealed an underlying lipomyelomeningocele with a tethered cord in the spinal canal. Histopathology of the right buttock cutaneous lesion was consistent with a diagnosis of RMH. Surgical excision was performed on the midline intradural lipoma and the lesion on the buttock was monitored clinically. Repeat biopsy of this site at 1 year of age revealed complete spontaneous regression. This case highlights three interesting features: the association with an occult spinal dysraphism lipomyelomeningocele and tethered cord, the clinical presentation of an atrophic plaque as opposed to the more commonly reported raised lesions, and the phenomenon of spontaneous regression of the lesion. Most importantly, this final feature of regression in our patient suggests that, in the absence of symptoms, clinical observation of RMH lesions is warranted for spontaneous regression for 1 to 2 years provided that no functional deficit is noted and that the cutaneous or deeper lesions are not causing a medical problem.
PMID: 24661237
ISSN: 0736-8046
CID: 933262
Novel candidate oncogenic drivers in pineoblastoma [Meeting Abstract]
ISI:000371597100272
ISSN: 1538-7445
CID: 2064382
Management of the Recurrence of Craniopharyngiomas
pp. 419-425
ISBN: 9780124167230
CID: 1842832
