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Targeted 595‐gene genomic profiling demonstrates low tumor mutational burden in olfactory neuroblastoma
Author(s) -
Friedman Jacob,
Schumacher Jane K.,
Papagiannopoulos Pete,
AlKhudari Samer,
Tajudeen Bobby A.,
Batra Pete S.
Publication year - 2021
Publication title -
international forum of allergy and rhinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.503
H-Index - 46
eISSN - 2042-6984
pISSN - 2042-6976
DOI - 10.1002/alr.22595
Subject(s) - esthesioneuroblastoma , medicine , immunotherapy , oncology , kras , malignancy , targeted therapy , cancer , radiation therapy , colorectal cancer
Background Olfactory neuroblastoma (ONB) is a rare skull‐base 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. Methods Retrospective chart review and next‐generation targeted 595‐gene 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. Results 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)‐approved targeted therapies. Conclusion TMB is a novel biomarker guiding the classification of neoplasms in the emerging era of immunotherapy. The characterization of ONB as a low‐TMB pathology contributes to the overall taxonomy of all cancers and suggests limited utility of immunotherapy treatment.