{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:52:09Z","timestamp":1791989529625,"version":"4.4.0"},"reference-count":57,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,11,22]],"date-time":"2016-11-22T00:00:00Z","timestamp":1479772800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Schnuck Markets Inc."},{"name":"St. Louis Men's Group Against Cancer"},{"name":"T32 Hematology Training Grant","award":["HL007088"],"award-info":[{"award-number":["HL007088"]}]},{"name":"SARC Career Development"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that arise at an estimated frequency of 8% to 13% in individuals with neurofibromatosis type 1 (NF1). Compared with their sporadic counterparts, NF1\u2010associated MPNSTs (NF1\u2010MPNSTs) develop in young adults, frequently recur (approximately 50% of cases), and carry a dismal prognosis. As such, most individuals affected with NF1\u2010MPNSTs die within 5 years of diagnosis, despite surgical resection combined with radiotherapy and chemotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Clinical genomic profiling was performed using 1000\u2009ng of DNA from 7 cases of NF1\u2010MPNST, and bioinformatic analyses were conducted to identify genes with actionable mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>A total of 3 women and 4 men with NF1\u2010MPNST were identified (median age, 38 years). Nonsynonymous mutations were discovered in 4 genes (neurofibromatosis type 1 [<jats:italic>NF1<\/jats:italic>], ROS proto\u2010oncogene 1 [<jats:italic>ROS1<\/jats:italic>], tumor protein p53 [<jats:italic>TP53<\/jats:italic>], and tyrosine kinase 2 [<jats:italic>TYK2<\/jats:italic>]), which in addition were mutated in other MPNST cases in this sample set. Consistent with their occurrence in individuals with NF1, all tumors had at least 1 mutation in the <jats:italic>NF1<\/jats:italic> gene. Whereas <jats:italic>TP53<\/jats:italic> gene mutations are frequently observed in other cancers, <jats:italic>ROS1<\/jats:italic> mutations are common in melanoma (15%\u201035%), another neural crest\u2010derived malignancy. In contrast, <jats:italic>TYK2<\/jats:italic> mutations are uncommon in other malignancies (&lt;7%). In the current series, recurrent <jats:italic>TYK2<\/jats:italic> mutations were identified in 2 cases of NF1\u2010MPNST (30% of cases), whereas TYK2 protein overexpression was observed in 60% of MPNST cases using an independently generated tissue microarray, regardless of NF1 status.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Clinical genomic analysis of the current series of NF1\u2010MPNST cases found that <jats:italic>TYK2<\/jats:italic> is a new gene mutated in MPNST. Future work will focus on examining the utility of TYK2 expression as a biomarker and therapeutic target for these cancers. <jats:bold><jats:italic>Cancer<\/jats:italic> 2017;123:1194\u20131201.<\/jats:bold> \u00a9 <jats:italic>2016 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.30455","type":"journal-article","created":{"date-parts":[[2016,11,22]],"date-time":"2016-11-22T14:12:50Z","timestamp":1479823970000},"page":"1194-1201","source":"Crossref","is-referenced-by-count":29,"title":["Clinical genomic profiling identifies <i>TYK2<\/i> mutation and overexpression in patients with neurofibromatosis type 1\u2010associated malignant peripheral nerve sheath tumors"],"prefix":"10.1002","volume":"123","author":[{"given":"Angela C.","family":"Hirbe","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine Washington University School of Medicine St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhurima","family":"Kaushal","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Washington University School of Medicine St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukesh Kumar","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Washington University School of Medicine St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonika","family":"Dahiya","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Washington University School of Medicine St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melike","family":"Pekmezci","sequence":"additional","affiliation":[{"name":"Department of Pathology University of California at San Francisco School of Medicine San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Perry","sequence":"additional","affiliation":[{"name":"Department of Pathology University of California at San Francisco School of Medicine San Francisco California"},{"name":"Department of Neurological Surgery University of California at San Francisco School of Medicine San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Gutmann","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,11,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/111.6.1355"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.045906"},{"key":"e_1_2_8_4_1","first-page":"1573","article-title":"International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis","volume":"62","author":"Ferner RE","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.5.311"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19900915)66:6<1253::AID-CNCR2820660627>3.0.CO;2-R"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19980601)82:11<2191::AID-CNCR14>3.0.CO;2-P"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0360-3016(98)00223-5"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24783"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13561"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.08.014"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2007.11.066"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-07-2335"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85183"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1609"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.01.074"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0081"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2641"},{"key":"e_1_2_8_19_1","first-page":"172","article-title":"USA, July 13\u201015, 1987","volume":"1","author":"National Institutes of Health Consensus Development Conference Statement: neurofibromatosis. 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