{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:40:32Z","timestamp":1790516432770,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,1,6]],"date-time":"2017-01-06T00:00:00Z","timestamp":1483660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006143","name":"Department of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006143","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pilocytic astrocytomas occur rarely in adults and show aggressive tumor behavior. However, their underlying molecular\u2010genetic events are largely uncharacterized. Hence, 59 adult pilocytic astrocytoma (APA) cases of classical histology were studied (MIB\u20101 LI: 1%\u20135%). Analysis of BRAF alterations using qRT\u2010PCR, confirmed KIAA1549\u2010BRAF fusion in 11 (19%) and BRAF\u2010gain in 2 (3.4%) cases. BRAF\u2010V600E mutation was noted in 1 (1.7%) case by sequencing. FGFR1\u2010mutation and FGFR\u2010TKD duplication were seen in 7\/59 (11.9%) and 3\/59 (5%) cases, respectively. Overall 36% of APAs harbored BRAF and\/or FGFR genetic alterations. Notably, FGFR related genetic alterations were enriched in tumors of supratentorial region (8\/25, 32%) as compared with other locations (<jats:italic>P<\/jats:italic>\u2009=\u20090.01). The difference in age of cases with FGFR1\u2010mutation (Mean age\u2009\u00b1\u2009SD: 37.2\u2009\u00b1\u200915 years) vs. KIAA1549\u2010BRAF fusion (Mean age\u2009\u00b1\u2009SD: 25.1\u2009\u00b1\u20094.1 years) was statistically significant (<jats:italic>P<\/jats:italic>\u2009=\u20090.03). Combined BRAF and FGFR alterations were identified in 3 (5%) cases. Notably, the cases with more than one genetic alteration were in higher age group (Mean age\u2009\u00b1\u2009SD: 50\u2009\u00b1\u200912 years) as compared with cases with single genetic alteration (Mean age\u2009\u00b1\u2009SD: 29\u2009\u00b1\u200910; <jats:italic>P<\/jats:italic>\u2009=\u20090.003). Immunopositivity of p\u2010MAPK\/p\u2010MEK1 was found in all the cases examined. The pS6\u2010immunoreactivity, a marker of mTOR activation was observed in 34\/39 (87%) cases. Interestingly, cases with BRAF and\/or FGFR related alteration showed significantly lower pS6\u2010immunostatining (3\/12; 25%) as compared with those with wild\u2010type BRAF and\/or FGFR (16\/27; 59%) (<jats:italic>P<\/jats:italic>\u2009=\u20090.04). Further, analysis of seven IDH wild\u2010type adult diffuse astrocytomas (DA) showed FGFR related genetic alterations in 43% cases. These and previous results suggest that APAs are genetically similar to IDH wild\u2010type adult DAs. APAs harbor infrequent BRAF alterations but more frequent FGFR alterations as compared with pediatric cases. KIAA1549\u2010BRAF fusion inversely correlates with increasing age whereas FGFR1\u2010mutation associates with older age. Activation of MAPK\/ERK\/mTOR signaling appears to be an important oncogenic event in APAs and may be underlying event of aggressive tumor behavior. The findings provided a rationale for potential therapeutic advantage of targeting MAPK\/ERK\/mTOR pathway in APAs.<\/jats:p>","DOI":"10.1111\/bpa.12444","type":"journal-article","created":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T15:03:53Z","timestamp":1473347033000},"page":"580-589","source":"Crossref","is-referenced-by-count":33,"title":["Genetic alterations related to <scp>BRAF\u2010FGFR<\/scp> genes and dysregulated <scp>MAPK\/ERK<\/scp>\/m<scp>TOR<\/scp> signaling in adult pilocytic astrocytoma"],"prefix":"10.1111","volume":"27","author":[{"given":"Pankaj","family":"Pathak","sequence":"first","affiliation":[{"name":"Department of Pathology All India Institute of Medical Sciences New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupam","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery All India Institute of Medical Sciences New Delhi 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India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishali","family":"Suri","sequence":"additional","affiliation":[{"name":"Department of Pathology All India Institute of Medical Sciences New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehar C.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pathology All India Institute of Medical Sciences New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitra","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Pathology All India Institute of Medical Sciences New Delhi 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