{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:22:13Z","timestamp":1785237733235,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"PSB"},{"name":"Springer"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Olfactory neuroblastoma (ONB) is a rare skull\u2010base malignancy associated with delayed local recurrence. Treatment options in recurrent disease are few and unreliable. We undertook analysis of the ONB exome and immune environment in order to identify potential future immunotherapy treatment options.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retrospective chart review and next\u2010generation targeted 595\u2010gene genomic profiling was performed on a cohort of 14 ONB cases utilizing Tempus proprietary DNA and RNA sequencing technology. Tempus analysis provided a measurement of tumor mutational burden (TMB) and composition of the immune cell infiltrate present in tumor samples. Clinically relevant genomic alterations and associated targeted therapies were identified using cancer.gov and clinicaltrials.gov. TMB was tested by univariate analysis against clinical stage, pathologic grade, recurrence risk, and immune cell infiltration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean age for the subjects was 50 years (range, 13 to 76 years) with a male:female ratio of 1:1. TMB for ONB samples ranged from 1.3 to 9.6 mutations\/megabase (Mb) with mean of 3.8 mutations\/Mb. Univariate analysis showed no association between TMB and tumor stage, pathologic grade, risk of recurrence, or immune cell infiltration. Genomic profile revealed that 6 of 13 tumors had genetic alterations with targeted therapies in clinical trials, whereas 1 tumor demonstrated KRAS Q61R mutation with U.S. Food and Drug Administration (FDA)\u2010approved targeted therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TMB is a novel biomarker guiding the classification of neoplasms in the emerging era of immunotherapy. The characterization of ONB as a low\u2010TMB pathology contributes to the overall taxonomy of all cancers and suggests limited utility of immunotherapy treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22595","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T18:59:31Z","timestamp":1592506771000},"page":"58-64","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Targeted 595\u2010gene genomic profiling demonstrates low tumor mutational burden in olfactory neuroblastoma"],"prefix":"10.1002","volume":"11","author":[{"given":"Jacob","family":"Friedman","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Rush Center for Skull Base and Pituitary Surgery Rush University Medical Center  Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane K.","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Rush Center for Skull Base and Pituitary Surgery Rush University Medical Center  Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pete","family":"Papagiannopoulos","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Rush Center for Skull Base and Pituitary Surgery Rush University Medical Center  Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samer","family":"Al\u2010Khudari","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Rush Center for Skull Base and Pituitary Surgery Rush University Medical Center  Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bobby A.","family":"Tajudeen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Rush Center for Skull Base and Pituitary Surgery Rush University Medical Center  Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pete S.","family":"Batra","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Rush Center for Skull Base and Pituitary Surgery Rush University Medical Center  Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-199305000-00002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/sajc.sajc_273_18"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOO.0000000000000220"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0804-2"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-015-0078-9"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191244"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000003536"},{"issue":"01","key":"e_1_2_7_9_1","first-page":"S1","article-title":"Expression of programmed cell death\u2010ligand 1 in esthesioneuroblastoma","volume":"79","author":"London NR","year":"2018","journal-title":"J Neurol Surg B Skull Base"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.09.047"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0312-8"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-0386"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26797"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-17-0135"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1087"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2016-0287"},{"key":"e_1_2_7_19_1","volume-title":"Genomics","author":"Archibald JM","year":"2018"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k3529"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0768-9"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9683"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3182037b76"}],"container-title":["International Forum of Allergy &amp; 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