Cargando…
Tumor genomic alterations in severe-combined immunodeficiency bare-lymphocyte syndrome genes are associated with high mutational burden and disproportional neo-antigen rates
The progression of cancer requires mutational adaptation to permit unrestrained proliferation. A fraction of cancer mutations are oncogenic drivers, while others are putative ‘passengers’ that do not contribute to oncogenesis. However, altered peptides arising from passenger mutations may bind MHCs...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503546/ https://www.ncbi.nlm.nih.gov/pubmed/31064401 http://dx.doi.org/10.1186/s40425-019-0584-2 |
_version_ | 1783416430338768896 |
---|---|
author | Wang, Yu Johnson, Douglas B. Lu, Steve Diaz, Luis A. Xu, Yaomin Balko, Justin M. |
author_facet | Wang, Yu Johnson, Douglas B. Lu, Steve Diaz, Luis A. Xu, Yaomin Balko, Justin M. |
author_sort | Wang, Yu |
collection | PubMed |
description | The progression of cancer requires mutational adaptation to permit unrestrained proliferation. A fraction of cancer mutations are oncogenic drivers, while others are putative ‘passengers’ that do not contribute to oncogenesis. However, altered peptides arising from passenger mutations may bind MHCs and activate non-self immunologic signals (i.e. neoantigens), thus requiring immunoediting for cancer persistence. Disruption of antigen processing machinery in tumor cells may diminish this requirement. Here, we show that rare mutations in antigen processing machinery are associated with high mutational burden and increased predicted neoantigen load, providing insights into the mechanisms of high mutation burden in some patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40425-019-0584-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6503546 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65035462019-05-10 Tumor genomic alterations in severe-combined immunodeficiency bare-lymphocyte syndrome genes are associated with high mutational burden and disproportional neo-antigen rates Wang, Yu Johnson, Douglas B. Lu, Steve Diaz, Luis A. Xu, Yaomin Balko, Justin M. J Immunother Cancer Short Report The progression of cancer requires mutational adaptation to permit unrestrained proliferation. A fraction of cancer mutations are oncogenic drivers, while others are putative ‘passengers’ that do not contribute to oncogenesis. However, altered peptides arising from passenger mutations may bind MHCs and activate non-self immunologic signals (i.e. neoantigens), thus requiring immunoediting for cancer persistence. Disruption of antigen processing machinery in tumor cells may diminish this requirement. Here, we show that rare mutations in antigen processing machinery are associated with high mutational burden and increased predicted neoantigen load, providing insights into the mechanisms of high mutation burden in some patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40425-019-0584-2) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-07 /pmc/articles/PMC6503546/ /pubmed/31064401 http://dx.doi.org/10.1186/s40425-019-0584-2 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Short Report Wang, Yu Johnson, Douglas B. Lu, Steve Diaz, Luis A. Xu, Yaomin Balko, Justin M. Tumor genomic alterations in severe-combined immunodeficiency bare-lymphocyte syndrome genes are associated with high mutational burden and disproportional neo-antigen rates |
title | Tumor genomic alterations in severe-combined immunodeficiency bare-lymphocyte syndrome genes are associated with high mutational burden and disproportional neo-antigen rates |
title_full | Tumor genomic alterations in severe-combined immunodeficiency bare-lymphocyte syndrome genes are associated with high mutational burden and disproportional neo-antigen rates |
title_fullStr | Tumor genomic alterations in severe-combined immunodeficiency bare-lymphocyte syndrome genes are associated with high mutational burden and disproportional neo-antigen rates |
title_full_unstemmed | Tumor genomic alterations in severe-combined immunodeficiency bare-lymphocyte syndrome genes are associated with high mutational burden and disproportional neo-antigen rates |
title_short | Tumor genomic alterations in severe-combined immunodeficiency bare-lymphocyte syndrome genes are associated with high mutational burden and disproportional neo-antigen rates |
title_sort | tumor genomic alterations in severe-combined immunodeficiency bare-lymphocyte syndrome genes are associated with high mutational burden and disproportional neo-antigen rates |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503546/ https://www.ncbi.nlm.nih.gov/pubmed/31064401 http://dx.doi.org/10.1186/s40425-019-0584-2 |
work_keys_str_mv | AT wangyu tumorgenomicalterationsinseverecombinedimmunodeficiencybarelymphocytesyndromegenesareassociatedwithhighmutationalburdenanddisproportionalneoantigenrates AT johnsondouglasb tumorgenomicalterationsinseverecombinedimmunodeficiencybarelymphocytesyndromegenesareassociatedwithhighmutationalburdenanddisproportionalneoantigenrates AT lusteve tumorgenomicalterationsinseverecombinedimmunodeficiencybarelymphocytesyndromegenesareassociatedwithhighmutationalburdenanddisproportionalneoantigenrates AT diazluisa tumorgenomicalterationsinseverecombinedimmunodeficiencybarelymphocytesyndromegenesareassociatedwithhighmutationalburdenanddisproportionalneoantigenrates AT xuyaomin tumorgenomicalterationsinseverecombinedimmunodeficiencybarelymphocytesyndromegenesareassociatedwithhighmutationalburdenanddisproportionalneoantigenrates AT balkojustinm tumorgenomicalterationsinseverecombinedimmunodeficiencybarelymphocytesyndromegenesareassociatedwithhighmutationalburdenanddisproportionalneoantigenrates |