{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:22:38Z","timestamp":1758709358336,"version":"3.37.3"},"reference-count":15,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,3,30]],"date-time":"2018-03-30T00:00:00Z","timestamp":1522368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tumor genome sequencing has become an invaluable resource in determining targets for new therapies. In this report, we describe the case of a patient with metastatic urothelial carcinoma with sarcomatoid features. Sarcomatoid differentiation is a rare histologic subtype that confers a more aggressive course. The first\u2010line treatment for patients with urothelial carcinoma is platinum\u2010based chemotherapy. Next generation tumor sequencing performed using the FoundationOne assay revealed loss of one <jats:italic>NF2<\/jats:italic> allele and an unbalanced der(22)t(10;22)(p11.22;q12.2) chromosomal rearrangement involving the other <jats:italic>NF2<\/jats:italic> allele, resulting in truncation and predicted loss of function. Fluorescence in situ hybridization (FISH) analysis confirmed the presence of one <jats:italic>NF2<\/jats:italic> signal. <jats:italic>NF2<\/jats:italic> mutations have been found in a variety of cancers and result in activation of the mTOR pathway. As such, the use of mTOR inhibitors, such as everolimus are thought to be particularly effective in the case of <jats:italic>NF2<\/jats:italic> loss. Our patient had a dramatic response to first\u2010line chemotherapy, but unfortunately experienced subsequent progression of his cancer and could not tolerate everolimus. Although our patient's tumor demonstrated unique acquired genetic features including both loss of heterozygosity and truncation of the <jats:italic>NF2<\/jats:italic> locus, he still achieved a meaningful response to platinum\u2010based chemotherapy.<\/jats:p>","DOI":"10.1002\/gcc.22537","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T10:38:00Z","timestamp":1521110280000},"page":"430-433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A prolonged response to platinum\u2010based therapy in a patient with metastatic urothelial carcinoma harboring a single rearranged and truncated <i>NF2<\/i> gene"],"prefix":"10.1002","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1370-3392","authenticated-orcid":false,"given":"Tala","family":"Achkar","sequence":"first","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Medicine University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"},{"name":"University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siraj M.","family":"Ali","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc Cambridge Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison","family":"Welsh","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc Cambridge Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajiv","family":"Dhir","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center Pittsburgh Pennsylvania"},{"name":"UPMC Genitourinary Pathology Center of Excellence and the Department of Pathology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5438-6808","authenticated-orcid":false,"given":"Susanne M.","family":"Gollin","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center Pittsburgh Pennsylvania"},{"name":"Department of Human Genetics University of Pittsburgh Graduate School of Public Health Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahul A.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Medicine University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"},{"name":"University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,30]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32455-2"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30616-2"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.01.015"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-014-1710-0"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1226344"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0353"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01578-08"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noq012"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/not242"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01581-08"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2015.11.008"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2015-0085-OA"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525735113"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.01.051"},{"key":"e_1_2_3_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.34.15_suppl.104"}],"container-title":["Genes, 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