Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis

Abstract Pancreatic Ductal AdenoCarcinoma (PDAC) represents about 90% of pancreatic cancers. It is one of the most aggressive cancer, with a 5-year survival rate below 10% due to late diagnosis and poor therapeutic efficiency. This bad prognosis thus encourages intense research in order to better un...

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Autores principales:	Sophie Liot, Naïma El Kholti, Jonathan Balas, Laurent Genestier, Bernard Verrier, Ulrich Valcourt, Elise Lambert
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b7de59685214b748379263377f07ace
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spelling	oai:doaj.org-article:9b7de59685214b748379263377f07ace2021-12-02T16:17:18ZDevelopment of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis10.1038/s41598-021-94566-x2045-2322https://doaj.org/article/9b7de59685214b748379263377f07ace2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94566-xhttps://doaj.org/toc/2045-2322Abstract Pancreatic Ductal AdenoCarcinoma (PDAC) represents about 90% of pancreatic cancers. It is one of the most aggressive cancer, with a 5-year survival rate below 10% due to late diagnosis and poor therapeutic efficiency. This bad prognosis thus encourages intense research in order to better understand PDAC pathogenesis and molecular basis leading to the development of innovative therapeutic strategies. This research frequently involves the KC (LSL:Kras G12D ;Pdx1-CRE) genetically engineered mouse model, which leads to pancreatic cancer predisposition. However, as frequently encountered in animal models, the KC mouse model also exhibits biases. Herein, we report a new adverse effect of Kras G12D mutation in KC mouse model. In our hands, 10% of KC mice developed clinical signs reaching pre-defined end-points between 100- and 150-days post-parturition, and associated with large thymic mass development. Histological and genetic analyses of this massive thymus enabled us (1) to characterize it as a highly proliferative thymic lymphoma and (2) to detect the unexpected recombination of the Lox-STOP-Lox cassette upstream Kras G12D allele and subsequent KRASG12D protein expression in all cells composing thymic masses. Finally, we highlighted that development of such thymic tumor was associated with accelerated pancreatic carcinogenesis, immune compartment disorganization, and in some cases, lung malignancies.Sophie LiotNaïma El KholtiJonathan BalasLaurent GenestierBernard VerrierUlrich ValcourtElise LambertNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sophie Liot Naïma El Kholti Jonathan Balas Laurent Genestier Bernard Verrier Ulrich Valcourt Elise Lambert Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis
description	Abstract Pancreatic Ductal AdenoCarcinoma (PDAC) represents about 90% of pancreatic cancers. It is one of the most aggressive cancer, with a 5-year survival rate below 10% due to late diagnosis and poor therapeutic efficiency. This bad prognosis thus encourages intense research in order to better understand PDAC pathogenesis and molecular basis leading to the development of innovative therapeutic strategies. This research frequently involves the KC (LSL:Kras G12D ;Pdx1-CRE) genetically engineered mouse model, which leads to pancreatic cancer predisposition. However, as frequently encountered in animal models, the KC mouse model also exhibits biases. Herein, we report a new adverse effect of Kras G12D mutation in KC mouse model. In our hands, 10% of KC mice developed clinical signs reaching pre-defined end-points between 100- and 150-days post-parturition, and associated with large thymic mass development. Histological and genetic analyses of this massive thymus enabled us (1) to characterize it as a highly proliferative thymic lymphoma and (2) to detect the unexpected recombination of the Lox-STOP-Lox cassette upstream Kras G12D allele and subsequent KRASG12D protein expression in all cells composing thymic masses. Finally, we highlighted that development of such thymic tumor was associated with accelerated pancreatic carcinogenesis, immune compartment disorganization, and in some cases, lung malignancies.
format	article
author	Sophie Liot Naïma El Kholti Jonathan Balas Laurent Genestier Bernard Verrier Ulrich Valcourt Elise Lambert
author_facet	Sophie Liot Naïma El Kholti Jonathan Balas Laurent Genestier Bernard Verrier Ulrich Valcourt Elise Lambert
author_sort	Sophie Liot
title	Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis
title_short	Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis
title_full	Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis
title_fullStr	Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis
title_full_unstemmed	Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis
title_sort	development of thymic tumor in [lsl:kras g12d ; pdx1-cre] mice, an adverse effect associated with accelerated pancreatic carcinogenesis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9b7de59685214b748379263377f07ace
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Development of thymic tumor in [LSL:Kras G12D ; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis

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