{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:49:46Z","timestamp":1787806186328,"version":"build-2784847793"},"reference-count":6,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,1,18]],"date-time":"2019-01-18T00:00:00Z","timestamp":1547769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Primary mediastinal nonseminomatous germ cell tumors (PMNSGCT) frequently become refractory to chemotherapy, and no effective salvage therapy exists. We performed genomic profiling on a series of 44 PMNSGCT and compared the results with those from chemorefractory, metastatic pure seminomatous (Sem, n = 22) and nonseminomatous (NS, n = 86) testicular germ cell tumors. Archival tissues were sequenced by a hybrid capture-based technology (FoundationONE; Foundation Medicine, Inc., Cambridge, MA). Microsatellite instability (MSI) and tumor mutational burden (TMB, mutations [mut]\/Mb) were determined.<\/jats:p>\n               <jats:p>Statistically significant differences in genomic alterations (GA) of PMNSGCT versus NS included higher TP53 pathway GA (p &amp;lt; .0001), PIK3CA pathway GA (p &amp;lt; .0001), and lower cell-cycle pathway GA (p = .0004). There were no MSI-high PMNSGCT cases. Mean TMB was similar between the groups, but there were more \u226510 mut\/Mb in the PMNSGCT group versus NS (11.4% vs. 4.6%).<\/jats:p>\n               <jats:p>The GA identified in PMNSGCT were similar to the findings from NS, with differential opportunities for targeted therapies and immunotherapies. Further study of precision treatments appears warranted.<\/jats:p>","DOI":"10.1634\/theoncologist.2018-0430","type":"journal-article","created":{"date-parts":[[2019,1,18]],"date-time":"2019-01-18T20:15:13Z","timestamp":1547842513000},"page":"e142-e145","source":"Crossref","is-referenced-by-count":27,"title":["Genomic Features for Therapeutic Insights of Chemotherapy-Resistant, Primary Mediastinal Nonseminomatous Germ Cell Tumors and Comparison with Gonadal Counterpart"],"prefix":"10.1093","volume":"24","author":[{"given":"Andrea","family":"Necchi","sequence":"first","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennady","family":"Bratslavsky","sequence":"additional","affiliation":[{"name":"Upstate Medical University, Syracuse, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Chung","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherri","family":"Millis","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie M.","family":"Gay","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siraj M.","family":"Ali","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Ross","sequence":"additional","affiliation":[{"name":"Upstate Medical University, Syracuse, New York, USA"},{"name":"Foundation Medicine, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,1,18]]},"reference":[{"key":"2021122506421403200_onco12826-bib-0001","doi-asserted-by":"crossref","first-page":"4906","DOI":"10.1200\/JCO.2009.26.8128","article-title":"Prognostic factors in patients with metastatic germ cell tumors who experienced treatment failure with cisplatin-based first-line chemotherapy","volume":"28","author":"International Prognostic Factors Study Group","year":"2010","journal-title":"J Clin Oncol"},{"key":"2021122506421403200_onco12826-bib-0002","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13073-017-0424-2","article-title":"Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden","volume":"9","author":"Chalmers","year":"2017","journal-title":"Genome Med"},{"issue":"suppl 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GU14-206","volume":"29","author":"Adra","year":"2018","journal-title":"Ann Oncol"},{"issue":"suppl 15","key":"2021122506421403200_onco12826-bib-0006","doi-asserted-by":"crossref","first-page":"4547a","DOI":"10.1200\/JCO.2018.36.15_suppl.4547","article-title":"Apache: An open label, randomized, phase 2 study of durvalumab (Durva), alone or in combination with tremelimumab (Treme), in patients (pts) with advanced germ cell tumors (GCT): Results at the end of first stage","volume":"36","author":"Raggi","year":"2018","journal-title":"J Clin Oncol"}],"container-title":["The 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