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Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden
Amplifications of oncogenic genes are often considered actionable. However, not all patients respond. Questions have therefore arisen regarding the degree to which amplifications, especially non-focal ones, mediate overexpression. We found that a subset of high-level gene amplifications (≥ 6 copies)...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638100/ https://www.ncbi.nlm.nih.gov/pubmed/34857015 http://dx.doi.org/10.1186/s13045-021-01211-1 |
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author | Boichard, Amélie Lippman, Scott M. Kurzrock, Razelle |
author_facet | Boichard, Amélie Lippman, Scott M. Kurzrock, Razelle |
author_sort | Boichard, Amélie |
collection | PubMed |
description | Amplifications of oncogenic genes are often considered actionable. However, not all patients respond. Questions have therefore arisen regarding the degree to which amplifications, especially non-focal ones, mediate overexpression. We found that a subset of high-level gene amplifications (≥ 6 copies) (from The Cancer Genome Atlas database) was not over-expressed at the RNA level. Unexpectedly, focal amplifications were more frequently silenced than non-focal amplifications. Most non-focal amplifications were not silenced; therefore, non-focal amplifications, if over-expressed, may be therapeutically tractable. Furthermore, specific silencing of high-level focal or non-focal gene amplifications may explain resistance to drugs that target the relevant gene product. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-021-01211-1. |
format | Online Article Text |
id | pubmed-8638100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86381002021-12-02 Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden Boichard, Amélie Lippman, Scott M. Kurzrock, Razelle J Hematol Oncol Letter to the Editor Amplifications of oncogenic genes are often considered actionable. However, not all patients respond. Questions have therefore arisen regarding the degree to which amplifications, especially non-focal ones, mediate overexpression. We found that a subset of high-level gene amplifications (≥ 6 copies) (from The Cancer Genome Atlas database) was not over-expressed at the RNA level. Unexpectedly, focal amplifications were more frequently silenced than non-focal amplifications. Most non-focal amplifications were not silenced; therefore, non-focal amplifications, if over-expressed, may be therapeutically tractable. Furthermore, specific silencing of high-level focal or non-focal gene amplifications may explain resistance to drugs that target the relevant gene product. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-021-01211-1. BioMed Central 2021-12-02 /pmc/articles/PMC8638100/ /pubmed/34857015 http://dx.doi.org/10.1186/s13045-021-01211-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Letter to the Editor Boichard, Amélie Lippman, Scott M. Kurzrock, Razelle Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden |
title | Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden |
title_full | Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden |
title_fullStr | Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden |
title_full_unstemmed | Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden |
title_short | Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden |
title_sort | therapeutic implications of cancer gene amplifications without mrna overexpression: silence may not be golden |
topic | Letter to the Editor |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638100/ https://www.ncbi.nlm.nih.gov/pubmed/34857015 http://dx.doi.org/10.1186/s13045-021-01211-1 |
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