Inflation of tumor mutation burden by tumor-only sequencing in under-represented groups

Abstract With the recent FDA approval of tumor mutational burden-high (TMB-H) status as a biomarker for treatment with a PD-1 inhibitor regardless of tumor type, accurate assessment of patient-specific TMB is more critical now more than ever. Using paired tumor and germline exome sequencing data fro...

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Autores principales:	Yan W. Asmann, Kaushal Parikh, P. Leif Bergsagel, Haidong Dong, Alex A. Adjei, Mitesh J. Borad, Aaron S. Mansfield
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/953d0fc861874af3a5542c24c24ac1b0
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spelling	oai:doaj.org-article:953d0fc861874af3a5542c24c24ac1b02021-12-02T16:30:41ZInflation of tumor mutation burden by tumor-only sequencing in under-represented groups10.1038/s41698-021-00164-52397-768Xhttps://doaj.org/article/953d0fc861874af3a5542c24c24ac1b02021-03-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00164-5https://doaj.org/toc/2397-768XAbstract With the recent FDA approval of tumor mutational burden-high (TMB-H) status as a biomarker for treatment with a PD-1 inhibitor regardless of tumor type, accurate assessment of patient-specific TMB is more critical now more than ever. Using paired tumor and germline exome sequencing data from 701 patients newly diagnosed with multiple myeloma, including 575 self-reported White patients and 126 self-reported Black patients, we observed that compared to the gold standard of filtering germline variants with patient-paired germline sequencing data, TMB estimates were significantly higher in both Black and White patients when using public databases for filtering non-somatic mutations; however, TMB was more significantly inflated in Black patients compared to White patients. TMB as a biomarker for patient selection to receive immune checkpoint inhibitors (ICIs) therapy without patient-paired germline sequencing may introduce racial bias due to the under-representation of minority groups in public databases.Yan W. AsmannKaushal ParikhP. Leif BergsagelHaidong DongAlex A. AdjeiMitesh J. BoradAaron S. MansfieldNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yan W. Asmann Kaushal Parikh P. Leif Bergsagel Haidong Dong Alex A. Adjei Mitesh J. Borad Aaron S. Mansfield Inflation of tumor mutation burden by tumor-only sequencing in under-represented groups
description	Abstract With the recent FDA approval of tumor mutational burden-high (TMB-H) status as a biomarker for treatment with a PD-1 inhibitor regardless of tumor type, accurate assessment of patient-specific TMB is more critical now more than ever. Using paired tumor and germline exome sequencing data from 701 patients newly diagnosed with multiple myeloma, including 575 self-reported White patients and 126 self-reported Black patients, we observed that compared to the gold standard of filtering germline variants with patient-paired germline sequencing data, TMB estimates were significantly higher in both Black and White patients when using public databases for filtering non-somatic mutations; however, TMB was more significantly inflated in Black patients compared to White patients. TMB as a biomarker for patient selection to receive immune checkpoint inhibitors (ICIs) therapy without patient-paired germline sequencing may introduce racial bias due to the under-representation of minority groups in public databases.
format	article
author	Yan W. Asmann Kaushal Parikh P. Leif Bergsagel Haidong Dong Alex A. Adjei Mitesh J. Borad Aaron S. Mansfield
author_facet	Yan W. Asmann Kaushal Parikh P. Leif Bergsagel Haidong Dong Alex A. Adjei Mitesh J. Borad Aaron S. Mansfield
author_sort	Yan W. Asmann
title	Inflation of tumor mutation burden by tumor-only sequencing in under-represented groups
title_short	Inflation of tumor mutation burden by tumor-only sequencing in under-represented groups
title_full	Inflation of tumor mutation burden by tumor-only sequencing in under-represented groups
title_fullStr	Inflation of tumor mutation burden by tumor-only sequencing in under-represented groups
title_full_unstemmed	Inflation of tumor mutation burden by tumor-only sequencing in under-represented groups
title_sort	inflation of tumor mutation burden by tumor-only sequencing in under-represented groups
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/953d0fc861874af3a5542c24c24ac1b0
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Inflation of tumor mutation burden by tumor-only sequencing in under-represented groups

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