{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T10:59:54Z","timestamp":1789901994375,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,2,23]],"date-time":"2016-02-23T00:00:00Z","timestamp":1456185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p>Pheochromocytomas (PCC) and abdominal paragangliomas (PGL) display a highly diverse genetic background and recent gene expression profiling studies have shown that PCC and PGL (together PPGL) alter either kinase signaling pathways or the pseudo\u2010hypoxia response pathway dependent of the genetic composition. Recurrent mutations in the <jats:italic>Harvey rat sarcoma viral oncogene homolog<\/jats:italic> (<jats:italic>HRAS<\/jats:italic>) have recently been verified in sporadic PPGLs. In order to further establish the <jats:italic>HRAS<\/jats:italic> mutation frequency and to characterize the associated expression profiles of <jats:italic>HRAS<\/jats:italic> mutated tumors, 156 PPGLs for exon 2 and 3 hotspot mutations in the <jats:italic>HRAS<\/jats:italic> gene was screened, and compared with microarray\u2010based gene expression profiles for 93 of the cases. The activating <jats:italic>HRAS<\/jats:italic> mutations G13R, Q61R, and Q61K were found in 10\/142 PCC (7.0%) and a Q61L mutation was revealed in 1\/14 PGL (7.1%). All <jats:italic>HRAS<\/jats:italic> mutated cases included in the mRNA expression profiling grouped in Cluster 2, and 21 transcripts were identified as altered when comparing the mutated tumors with 91 <jats:italic>HRAS<\/jats:italic> wild\u2010type PPGL. Somatic <jats:italic>HRAS<\/jats:italic> mutations were not revealed in cases with known PPGL susceptibility gene mutations and all <jats:italic>HRAS<\/jats:italic> mutated cases were benign. The <jats:italic>HRAS<\/jats:italic> mutation prevalence of all PPGL published up to date is 5.2% (49\/950), and 8.8% (48\/548) among cases without a known PPGL susceptibility gene mutation. The findings support a role of <jats:italic>HRAS<\/jats:italic> mutations as a somatic driver event in benign PPGL without other known susceptibility gene mutations. <jats:italic>HRAS<\/jats:italic> mutated PPGL cluster together with <jats:italic>NF1<\/jats:italic>\u2010 and <jats:italic>RET<\/jats:italic>\u2010mutated tumors associated with activation of kinase\u2010signaling pathways. \u00a9 2016 The Authors Genes, Chromosomes &amp; Cancer Published by Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22347","type":"journal-article","created":{"date-parts":[[2016,1,16]],"date-time":"2016-01-16T18:14:58Z","timestamp":1452968098000},"page":"452-459","source":"Crossref","is-referenced-by-count":30,"title":["<scp><i>HRAS<\/i><\/scp> mutation prevalence and associated expression patterns in pheochromocytoma"],"prefix":"10.1002","volume":"55","author":[{"given":"Adam","family":"Stenman","sequence":"first","affiliation":[{"name":"Department of Oncology and Pathology Karolinska Institutet Stockholm SE\u201017176 Sweden"},{"name":"Cancer Center Karolinska, CCK Karolinska University Hospital Solna Stockholm SE\u2010171 76 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Welander","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health Sciences Link\u00f6ping University Link\u00f6ping SE\u2010581 85 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Gustavsson","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health Sciences Link\u00f6ping University Link\u00f6ping SE\u2010581 85 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Brunaud","sequence":"additional","affiliation":[{"name":"Department of Digestive, Hepato\u2010Biliary and Endocrine Surgery, CHU Nancy \u2013 Hospital Brabois Adultes University De Lorraine Vandoeuvre\u2010les\u2010Nancy F\u201054511 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"B\u00e4ckdahl","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm SE\u2010171 76 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"S\u00f6derkvist","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health Sciences Link\u00f6ping University Link\u00f6ping SE\u2010581 85 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Gimm","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health Sciences Link\u00f6ping University Link\u00f6ping SE\u2010581 85 Sweden"},{"name":"Department of Surgery Region \u00d6sterg\u00f6tland Link\u00f6ping SE\u201058185 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Christofer","family":"Juhlin","sequence":"additional","affiliation":[{"name":"Department of Oncology and Pathology Karolinska Institutet Stockholm SE\u201017176 Sweden"},{"name":"Cancer Center Karolinska, CCK Karolinska University Hospital Solna Stockholm SE\u2010171 76 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"Larsson","sequence":"additional","affiliation":[{"name":"Department of Oncology and Pathology Karolinska Institutet Stockholm SE\u201017176 Sweden"},{"name":"Cancer Center Karolinska, CCK Karolinska University Hospital Solna Stockholm SE\u2010171 76 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2007.12.040"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.26686"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/bio.2013.0038"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/303072a0"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr324"},{"key":"e_1_2_6_8_1","first-page":"107","article-title":"Whole\u2010exome sequencing identifies MDH2 as a new familial paraganglioma gene","volume":"11","author":"Casc\u00f3n A","year":"2015","journal-title":"J Natl Cancer Inst"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7044"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.861"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-4257"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2804"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3648"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0010008"},{"key":"e_1_2_6_15_1","first-page":"147","volume-title":"World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Endocrine Organs","author":"DeLellis RA","year":"2004"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1677\/erc.1.00838"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7140"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22267"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.04.018"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-14-0016"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/138573"},{"key":"e_1_2_6_22_1","first-page":"1596","article-title":"Low frequency of ras gene mutations in neuroblastomas, pheochromocytomas, and medullary thyroid cancers","volume":"51","author":"Moley JF","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206763"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3879"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1648608"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1105358"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12006"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009641"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-4375"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-13-0384"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1992.tb02722.x"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgcc.22347","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.22347","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/gcc.22347","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.22347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T14:11:18Z","timestamp":1696601478000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.22347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,23]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1002\/gcc.22347"],"URL":"https:\/\/doi.org\/10.1002\/gcc.22347","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,23]]}}}