Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden

Abstract 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 (≥ ...

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Autores principales:	Amélie Boichard, Scott M. Lippman, Razelle Kurzrock
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Gene amplification mRNA expression Therapeutic actionability Diseases of the blood and blood-forming organs RC633-647.5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/95185bae2d454ef591c897621f0ee840
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spelling	oai:doaj.org-article:95185bae2d454ef591c897621f0ee8402021-12-05T12:03:29ZTherapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden10.1186/s13045-021-01211-11756-8722https://doaj.org/article/95185bae2d454ef591c897621f0ee8402021-12-01T00:00:00Zhttps://doi.org/10.1186/s13045-021-01211-1https://doaj.org/toc/1756-8722Abstract 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.Amélie BoichardScott M. LippmanRazelle KurzrockBMCarticleGene amplificationmRNA expressionTherapeutic actionabilityDiseases of the blood and blood-forming organsRC633-647.5Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of Hematology & Oncology, Vol 14, Iss 1, Pp 1-4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Gene amplification mRNA expression Therapeutic actionability Diseases of the blood and blood-forming organs RC633-647.5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Gene amplification mRNA expression Therapeutic actionability Diseases of the blood and blood-forming organs RC633-647.5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Amélie Boichard Scott M. Lippman Razelle Kurzrock Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden
description	Abstract 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.
format	article
author	Amélie Boichard Scott M. Lippman Razelle Kurzrock
author_facet	Amélie Boichard Scott M. Lippman Razelle Kurzrock
author_sort	Amélie Boichard
title	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_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_sort	therapeutic implications of cancer gene amplifications without mrna overexpression: silence may not be golden
publisher	BMC
publishDate	2021
url	https://doaj.org/article/95185bae2d454ef591c897621f0ee840
work_keys_str_mv	AT amelieboichard therapeuticimplicationsofcancergeneamplificationswithoutmrnaoverexpressionsilencemaynotbegolden AT scottmlippman therapeuticimplicationsofcancergeneamplificationswithoutmrnaoverexpressionsilencemaynotbegolden AT razellekurzrock therapeuticimplicationsofcancergeneamplificationswithoutmrnaoverexpressionsilencemaynotbegolden
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Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden

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