Context-dependent effects of whole-genome duplication during mammary tumor recurrence

Abstract Whole-genome duplication (WGD) generates polyploid cells possessing more than two copies of the genome and is among the most common genetic abnormalities in cancer. The frequency of WGD increases in advanced and metastatic tumors, and WGD is associated with poor prognosis in diverse tumor t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Rachel Newcomb, Emily Dean, Brock J. McKinney, James V. Alvarez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/697de7b1dc5d4dff8c6dee6e6e68404d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:697de7b1dc5d4dff8c6dee6e6e68404d
record_format	dspace
spelling	oai:doaj.org-article:697de7b1dc5d4dff8c6dee6e6e68404d2021-12-02T17:55:09ZContext-dependent effects of whole-genome duplication during mammary tumor recurrence10.1038/s41598-021-94332-z2045-2322https://doaj.org/article/697de7b1dc5d4dff8c6dee6e6e68404d2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94332-zhttps://doaj.org/toc/2045-2322Abstract Whole-genome duplication (WGD) generates polyploid cells possessing more than two copies of the genome and is among the most common genetic abnormalities in cancer. The frequency of WGD increases in advanced and metastatic tumors, and WGD is associated with poor prognosis in diverse tumor types, suggesting a functional role for polyploidy in tumor progression. Experimental evidence suggests that polyploidy has both tumor-promoting and suppressing effects, but how polyploidy regulates tumor progression remains unclear. Using a genetically engineered mouse model of Her2-driven breast cancer, we explored the prevalence and consequences of whole-genome duplication during tumor growth and recurrence. While primary tumors in this model are invariably diploid, nearly 40% of recurrent tumors undergo WGD. WGD in recurrent tumors was associated with increased chromosomal instability, decreased proliferation and increased survival in stress conditions. The effects of WGD on tumor growth were dependent on tumor stage. Surprisingly, in recurrent tumor cells WGD slowed tumor formation, growth rate and opposed the process of recurrence, while WGD promoted the growth of primary tumors. These findings highlight the importance of identifying conditions that promote the growth of polyploid tumors, including the cooperating genetic mutations that allow cells to overcome the barriers to WGD tumor cell growth and proliferation.Rachel NewcombEmily DeanBrock J. McKinneyJames V. AlvarezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rachel Newcomb Emily Dean Brock J. McKinney James V. Alvarez Context-dependent effects of whole-genome duplication during mammary tumor recurrence
description	Abstract Whole-genome duplication (WGD) generates polyploid cells possessing more than two copies of the genome and is among the most common genetic abnormalities in cancer. The frequency of WGD increases in advanced and metastatic tumors, and WGD is associated with poor prognosis in diverse tumor types, suggesting a functional role for polyploidy in tumor progression. Experimental evidence suggests that polyploidy has both tumor-promoting and suppressing effects, but how polyploidy regulates tumor progression remains unclear. Using a genetically engineered mouse model of Her2-driven breast cancer, we explored the prevalence and consequences of whole-genome duplication during tumor growth and recurrence. While primary tumors in this model are invariably diploid, nearly 40% of recurrent tumors undergo WGD. WGD in recurrent tumors was associated with increased chromosomal instability, decreased proliferation and increased survival in stress conditions. The effects of WGD on tumor growth were dependent on tumor stage. Surprisingly, in recurrent tumor cells WGD slowed tumor formation, growth rate and opposed the process of recurrence, while WGD promoted the growth of primary tumors. These findings highlight the importance of identifying conditions that promote the growth of polyploid tumors, including the cooperating genetic mutations that allow cells to overcome the barriers to WGD tumor cell growth and proliferation.
format	article
author	Rachel Newcomb Emily Dean Brock J. McKinney James V. Alvarez
author_facet	Rachel Newcomb Emily Dean Brock J. McKinney James V. Alvarez
author_sort	Rachel Newcomb
title	Context-dependent effects of whole-genome duplication during mammary tumor recurrence
title_short	Context-dependent effects of whole-genome duplication during mammary tumor recurrence
title_full	Context-dependent effects of whole-genome duplication during mammary tumor recurrence
title_fullStr	Context-dependent effects of whole-genome duplication during mammary tumor recurrence
title_full_unstemmed	Context-dependent effects of whole-genome duplication during mammary tumor recurrence
title_sort	context-dependent effects of whole-genome duplication during mammary tumor recurrence
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/697de7b1dc5d4dff8c6dee6e6e68404d
work_keys_str_mv	AT rachelnewcomb contextdependenteffectsofwholegenomeduplicationduringmammarytumorrecurrence AT emilydean contextdependenteffectsofwholegenomeduplicationduringmammarytumorrecurrence AT brockjmckinney contextdependenteffectsofwholegenomeduplicationduringmammarytumorrecurrence AT jamesvalvarez contextdependenteffectsofwholegenomeduplicationduringmammarytumorrecurrence
_version_	1718379111826587648

Context-dependent effects of whole-genome duplication during mammary tumor recurrence

Ejemplares similares