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Michael E. Sughrue, Ari J. Kane, Gopal Shangari, Andrew T. Parsa, Mitchel S. Berger and Michael W. McDermott

meningiomas . Kaohsiung J Med Sci 19 : 334 – 338 , 2003 24 Xiao GH , Chernoff J , Testa JR : NF2: the wizardry of merlin . Genes Chromosomes Cancer 38 : 389 – 399 , 2003 25 Xing M : BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications . Endocr Rev 28 : 742 – 762 , 2007

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Michael M. H. Yang, Ash Singhal, Shahrad Rod Rassekh, Stephen Yip, Patrice Eydoux and Christopher Dunham

antigen in pleomorphic xanthoastrocytomas . Acta Neuropathol 105 : 358 – 364 , 2003 24 Sanders RP , Kocak M , Burger PC , Merchant TE , Gajjar A , Broniscer A : High-grade astrocytoma in very young children . Pediatr Blood Cancer 49 : 888 – 893 , 2007 25 Schiffman JD , Hodgson JG , VandenBerg SR , Flaherty P , Polley MYC , Yu M , : Oncogenic BRAF mutation with CDKN2A inactivation is characteristic of a subset of pediatric malignant astrocytomas . Cancer Res 70 : 512 – 519 , 2010 26 Schindler G , Capper D

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Gavin P. Dunn, Ovidiu C. Andronesi and Daniel P. Cahill

inhibiting the mutant enzyme would make these tumors behave like their more aggressive WT counterparts. The differences in survival most likely stem from the fact that IDH1- mutant and -WT tumors arise from distinct lineages and ontogenies and thus represent entirely different neoplastic disease processes. Because gliomas acquire the IDH1 mutation very early in their development, akin to BRAF mutations in dysplastic nevi and melanoma, we envisage that it similarly represents a targetable dependency. From a surgical standpoint, it will be important to determine

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Nicholas F. Marko and Robert J. Weil

chromosomes 1, 15, 20, and 22. 152 Many molecular features that are commonly observed in other WHO Grade II gliomas are generally absent in PXAs. TP53 mutations are uncommon; 35 , 75 , 110 , 126 , 204 EGFR overexpression is absent; 50 LOH on chromosome 1, 8p, 9p, 10, 17, 19q, and 22q are only rarely observed; 75 , 126 and deletions or epigenomic inactivation involving CDKN2A or CDKN2B are inconsistent (although potentially functionally significant). 75 , 191 Conversely, BRAF mutations (particularly at the V600E “hot spot”) are common in PXA, 25 , 111 , 154

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Atsushi Kanoke, Masayuki Kanamori, Toshihiro Kumabe, Ryuta Saito, Mika Watanabe and Teiji Tominaga

from that of classic pilocytic astrocytoma. Because the primary pilocytic astrocytoma did not carry the BRAF V600E mutation, pilocytic astrocytoma and oligodendroglioma-like component in the first recurrent tissue had a different cell origin, or the amplification of BRAF was negatively selected under “de novo” BRAF V600E mutation. Second, we investigated the mechanism for the occurrence of metachronous, multicentric glioma, based on the analysis for IDH1 and BRAF mutation and BRAF amplification. Previously, differences and similarities in genetic

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without written permission from JNSPG. 2014 Introduction Pediatric low grade astrocytomas are a diverse group of tumors. We have previously shown that pediatric gliomas have BRAF mutations, specifically a BRAF V600E mutation and BRAF fusion genes. KIAA1549 was the first fusion partner identified in gliomas and recently several other partners have been found. BRAF inhibitors showed exciting results in treating V600E-dependent melanomas. We investigated the efficacy of the BRAF inhibitor PLX4720 against

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Masayuki Kanamori, Atsuo Kikuchi, Mika Watanabe, Ichiyo Shibahara, Ryuta Saito, Yoji Yamashita, Yukihiko Sonoda, Toshihiro Kumabe, Shigeo Kure and Teiji Tominaga

system tumors . Arch Pathol Lab Med 131 : 1532 – 1540 , 2007 22 Roessler K , Dietrich W , Kitz K : High diagnostic accuracy of cytologic smears of central nervous system tumors. A 15-year experience based on 4,172 patients . Acta Cytol 46 : 667 – 674 , 2002 23 Schiffman JD , Hodgson JG , VandenBerg SR , Flaherty P , Polley MY , Yu M , : Oncogenic BRAF mutation with CDKN2A inactivation is characteristic of a subset of pediatric malignant astrocytomas . Cancer Res 70 : 512 – 519 , 2010 24 Schindler G , Capper D , Meyer

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Darryl Lau, Stephen T. Magill and Manish K. Aghi

C , Hu X , Rosenblum MK , Koutcher JA , Holland EC : Dose-dependent effects of platelet-derived growth factor-B on glial tumorigenesis . Cancer Res 64 : 4783 – 4789 , 2004 95 Smalley KS , Xiao M , Villanueva J , Nguyen TK , Flaherty KT , Letrero R , : CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations . Oncogene 28 : 85 – 94 , 2009 96 Stommel JM , Kimmelman AC , Ying H , Nabioullin R , Ponugoti AH , Wiedemeyer R , : Coactivation of receptor tyrosine kinases affects the

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Ahmed K. Alomari, Brian J. Kelley, Eyiyemisi Damisah, Asher Marks, Pei Hui, Michael DiLuna and Alexander Vortmeyer

failed to show convincing evidence of the presence of the β-catenin or BRAF mutation. Although a recent meta-analysis of 109 studies and 531 unique cases of craniopharyngioma found that patients who underwent subtotal resection and did not receive radiation therapy had a worse outcome than patients who underwent gross-total resection or those who had subtotal resection and were also treated with radiation therapy, 4 a decision was made to follow up our patient with serial MRI and to initiate radiation therapy only if there were concerns of recurrence. This was based

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Pamela S. Jones, Daniel P. Cahill, Priscilla K. Brastianos, Keith T. Flaherty and William T. Curry

information was obtained: date of birth; sex; date of primary melanoma diagnosis; number of cerebral metastases; date(s) of craniotomy; date(s) and dose(s) of ipilimumab; radiation therapy type, dose(s), and date(s); neurological examination findings; operative note(s); pathology, including BRAF mutation status; and neurosurgical and oncological visit notes. Improvements in performance status were noted as “no change,” “improved,” or “worsened,” based on comparison of preoperative and postoperative notes. Corticosteroid dependence was determined by duration and magnitude