High tumor amplification burden is associated with TP53 mutations in the pan-cancer setting

Next-generation sequencing data is fundamentally changing the clinical management of patients with cancer. The most frequent genomic alterations in malignancy are mutations and amplifications, with a subset of tumors having multiple amplifications – “amplificators”. We sought to understand the molec...

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Main Authors: Rushikesh S. Joshi, Amelie Boichard, Jacob J. Adashek, Razelle Kurzrock
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Cancer Biology & Therapy
Subjects:
Online Access:http://dx.doi.org/10.1080/15384047.2022.2128608
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author Rushikesh S. Joshi
Amelie Boichard
Jacob J. Adashek
Razelle Kurzrock
author_facet Rushikesh S. Joshi
Amelie Boichard
Jacob J. Adashek
Razelle Kurzrock
author_sort Rushikesh S. Joshi
collection DOAJ
description Next-generation sequencing data is fundamentally changing the clinical management of patients with cancer. The most frequent genomic alterations in malignancy are mutations and amplifications, with a subset of tumors having multiple amplifications – “amplificators”. We sought to understand the molecular correlates of high tumor amplification burden in a pan-cancer context. Using both national registries and a single-institution dataset, our results demonstrate that cancers with TP53 mutations (as compared to those with wild-type TP53) exhibited significantly higher tumor amplification burden across all datasets. Amplifications, generally associated with overexpression, may be potentially actionable secondary consequences of TP53 mutations.
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spelling doaj.art-56cd5d1096b14a908af6891a13a48c192023-12-05T15:58:14ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762022-12-012311610.1080/15384047.2022.21286082128608High tumor amplification burden is associated with TP53 mutations in the pan-cancer settingRushikesh S. Joshi0Amelie Boichard1Jacob J. Adashek2Razelle Kurzrock3University of California San DiegoUniversity of Strasbourg HospitalsThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins HospitalMedical College of WisconsinNext-generation sequencing data is fundamentally changing the clinical management of patients with cancer. The most frequent genomic alterations in malignancy are mutations and amplifications, with a subset of tumors having multiple amplifications – “amplificators”. We sought to understand the molecular correlates of high tumor amplification burden in a pan-cancer context. Using both national registries and a single-institution dataset, our results demonstrate that cancers with TP53 mutations (as compared to those with wild-type TP53) exhibited significantly higher tumor amplification burden across all datasets. Amplifications, generally associated with overexpression, may be potentially actionable secondary consequences of TP53 mutations.http://dx.doi.org/10.1080/15384047.2022.2128608cancer genesnext-generation sequencingamplificationstp53
spellingShingle Rushikesh S. Joshi
Amelie Boichard
Jacob J. Adashek
Razelle Kurzrock
High tumor amplification burden is associated with TP53 mutations in the pan-cancer setting
Cancer Biology & Therapy
cancer genes
next-generation sequencing
amplifications
tp53
title High tumor amplification burden is associated with TP53 mutations in the pan-cancer setting
title_full High tumor amplification burden is associated with TP53 mutations in the pan-cancer setting
title_fullStr High tumor amplification burden is associated with TP53 mutations in the pan-cancer setting
title_full_unstemmed High tumor amplification burden is associated with TP53 mutations in the pan-cancer setting
title_short High tumor amplification burden is associated with TP53 mutations in the pan-cancer setting
title_sort high tumor amplification burden is associated with tp53 mutations in the pan cancer setting
topic cancer genes
next-generation sequencing
amplifications
tp53
url http://dx.doi.org/10.1080/15384047.2022.2128608
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