Enhanced Rate of Acquisition of Point Mutations in Mouse Intestinal Adenomas Compared to Normal Tissue
The most prevalent single-nucleotide substitution (SNS) found in cancers is a C-to-T substitution in the CpG motif. It has been proposed that many of these SNSs arise during organismal aging, prior to transformation of a normal cell into a precancerous/cancer cell. Here, we isolated single intestina...
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doaj-9b2908d376e54d3a867825a9c3a0488a2020-11-24T21:36:16ZengElsevierCell Reports2211-12472017-06-0119112185219210.1016/j.celrep.2017.05.051Enhanced Rate of Acquisition of Point Mutations in Mouse Intestinal Adenomas Compared to Normal TissueNatalia Lugli0Vasilis S. Dionellis1Paloma Ordóñez-Morán2Irene Kamileri3Sotirios K. Sotiriou4Joerg Huelsken5Thanos D. Halazonetis6Department of Molecular Biology, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Molecular Biology, University of Geneva, 1211 Geneva, SwitzerlandCancer Stem Cell Laboratory, Swiss Institute of Technology Lausanne (EPFL), ISREC, 1015 Lausanne, SwitzerlandDepartment of Molecular Biology, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Molecular Biology, University of Geneva, 1211 Geneva, SwitzerlandCancer Stem Cell Laboratory, Swiss Institute of Technology Lausanne (EPFL), ISREC, 1015 Lausanne, SwitzerlandDepartment of Molecular Biology, University of Geneva, 1211 Geneva, SwitzerlandThe most prevalent single-nucleotide substitution (SNS) found in cancers is a C-to-T substitution in the CpG motif. It has been proposed that many of these SNSs arise during organismal aging, prior to transformation of a normal cell into a precancerous/cancer cell. Here, we isolated single intestinal crypts derived from normal tissue or from adenomas of Apcmin/+ mice, expanded them minimally in vitro as organoids, and performed exome sequencing to identify point mutations that had been acquired in vivo at the single-cell level. SNSs, most of them being CpG-to-TpG substitutions, were at least ten times more frequent in adenoma than normal cells. Thus, contrary to the view that substitutions of this type are present due to normal-cell aging, the acquisition of point mutations increases upon transformation of a normal intestinal cell into a precancerous cell.http://www.sciencedirect.com/science/article/pii/S2211124717307088precancerous lesionsAPCadenomasorganoidsmutational signatures |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Natalia Lugli Vasilis S. Dionellis Paloma Ordóñez-Morán Irene Kamileri Sotirios K. Sotiriou Joerg Huelsken Thanos D. Halazonetis |
spellingShingle |
Natalia Lugli Vasilis S. Dionellis Paloma Ordóñez-Morán Irene Kamileri Sotirios K. Sotiriou Joerg Huelsken Thanos D. Halazonetis Enhanced Rate of Acquisition of Point Mutations in Mouse Intestinal Adenomas Compared to Normal Tissue Cell Reports precancerous lesions APC adenomas organoids mutational signatures |
author_facet |
Natalia Lugli Vasilis S. Dionellis Paloma Ordóñez-Morán Irene Kamileri Sotirios K. Sotiriou Joerg Huelsken Thanos D. Halazonetis |
author_sort |
Natalia Lugli |
title |
Enhanced Rate of Acquisition of Point Mutations in Mouse Intestinal Adenomas Compared to Normal Tissue |
title_short |
Enhanced Rate of Acquisition of Point Mutations in Mouse Intestinal Adenomas Compared to Normal Tissue |
title_full |
Enhanced Rate of Acquisition of Point Mutations in Mouse Intestinal Adenomas Compared to Normal Tissue |
title_fullStr |
Enhanced Rate of Acquisition of Point Mutations in Mouse Intestinal Adenomas Compared to Normal Tissue |
title_full_unstemmed |
Enhanced Rate of Acquisition of Point Mutations in Mouse Intestinal Adenomas Compared to Normal Tissue |
title_sort |
enhanced rate of acquisition of point mutations in mouse intestinal adenomas compared to normal tissue |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-06-01 |
description |
The most prevalent single-nucleotide substitution (SNS) found in cancers is a C-to-T substitution in the CpG motif. It has been proposed that many of these SNSs arise during organismal aging, prior to transformation of a normal cell into a precancerous/cancer cell. Here, we isolated single intestinal crypts derived from normal tissue or from adenomas of Apcmin/+ mice, expanded them minimally in vitro as organoids, and performed exome sequencing to identify point mutations that had been acquired in vivo at the single-cell level. SNSs, most of them being CpG-to-TpG substitutions, were at least ten times more frequent in adenoma than normal cells. Thus, contrary to the view that substitutions of this type are present due to normal-cell aging, the acquisition of point mutations increases upon transformation of a normal intestinal cell into a precancerous cell. |
topic |
precancerous lesions APC adenomas organoids mutational signatures |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717307088 |
work_keys_str_mv |
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