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Up to 40% of the cases are caused by germline mutations in one of at least 15 susceptibility genes, making them the human neoplasms with the highest degree of heritability. Recurrent somatic alterations are found in about 50% of the more common sporadic tumors with <jats:italic>NF1<\/jats:italic> being the most common mutated gene (20\u201325%). In many sporadic tumors, however, a genetic explanation is still lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>We investigated the genomic landscape of sporadic pheochromocytomas with whole\u2010exome sequencing of 16 paired tumor and normal DNA samples and extended confirmation analysis in 2 additional cohorts comprising a total of 80 sporadic pheochromocytomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We discovered on average 33\u00a0non\u2010silent somatic variants per tumor. One of the recurrently mutated genes was <jats:italic>FGFR1<\/jats:italic>, encoding the fibroblast growth factor receptor 1, which was recently revealed as an oncogene in pediatric brain tumors. Including a subsequent analysis of a larger cohort, activating <jats:italic>FGFR1<\/jats:italic> mutations were detected in three of 80 sporadic pheochromocytomas (3.8%). Gene expression microarray profiling showed that these tumors clustered with <jats:italic>NF1<\/jats:italic>\u2010, <jats:italic>RET,<\/jats:italic>\u2010 and <jats:italic>HRAS<\/jats:italic>\u2010mutated pheochromocytomas, indicating activation of the MAPK and PI3K\u2010AKT signal transduction pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Besides <jats:italic>RET<\/jats:italic> and <jats:italic>HRAS<\/jats:italic>, <jats:italic>FGFR1<\/jats:italic> is only the third protooncogene found to be recurrently mutated in pheochromocytomas. The results advance our biological understanding of pheochromocytoma and suggest that somatic <jats:italic>FGFR1<\/jats:italic> activation is an important event in a subset of sporadic pheochromocytomas.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s00268-017-4320-0","type":"journal-article","created":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T19:15:36Z","timestamp":1511205336000},"page":"482-489","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Activating <i>FGFR1<\/i> Mutations in Sporadic Pheochromocytomas"],"prefix":"10.1002","volume":"42","author":[{"given":"Jenny","family":"Welander","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences Link\u00f6ping University 58185 Link\u00f6ping 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