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Genomic heterogeneity in pancreatic cancer organoids and its stability with culture

The establishment of patient-derived pancreatic cancer organoid culture in recent years creates an exciting opportunity for researchers to perform a wide range of in vitro studies on a model that closely recapitulates the tumor. One of the outstanding question in pancreatic cancer biology is the cau...

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Autores principales: Usman, Olalekan H., Zhang, Liting, Xie, Gengqiang, Kocher, Hemant M., Hwang, Chang-il, Wang, Yue Julia, Mallory, Xian, Irianto, Jerome
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763422/
https://www.ncbi.nlm.nih.gov/pubmed/36535941
http://dx.doi.org/10.1038/s41525-022-00342-9
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author Usman, Olalekan H.
Zhang, Liting
Xie, Gengqiang
Kocher, Hemant M.
Hwang, Chang-il
Wang, Yue Julia
Mallory, Xian
Irianto, Jerome
author_facet Usman, Olalekan H.
Zhang, Liting
Xie, Gengqiang
Kocher, Hemant M.
Hwang, Chang-il
Wang, Yue Julia
Mallory, Xian
Irianto, Jerome
author_sort Usman, Olalekan H.
collection PubMed
description The establishment of patient-derived pancreatic cancer organoid culture in recent years creates an exciting opportunity for researchers to perform a wide range of in vitro studies on a model that closely recapitulates the tumor. One of the outstanding question in pancreatic cancer biology is the causes and consequences of genomic heterogeneity observed in the disease. However, to use pancreatic cancer organoids as a model to study genomic variations, we need to first understand the degree of genomic heterogeneity and its stability within organoids. Here, we used single-cell whole-genome sequencing to investigate the genomic heterogeneity of two independent pancreatic cancer organoid lines, as well as their genomic stability with extended culture. Clonal populations with similar copy number profiles were observed within the organoids, and the proportion of these clones was shifted with extended culture, suggesting the growth advantage of some clones. However, sub-clonal genomic heterogeneity was also observed within each clonal population, indicating the genomic instability of the pancreatic cancer cells themselves. Furthermore, our transcriptomic analysis also revealed a positive correlation between copy number alterations and gene expression regulation, suggesting the “gene dosage” effect of these copy number alterations that translates to gene expression regulation.
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spelling pubmed-97634222022-12-21 Genomic heterogeneity in pancreatic cancer organoids and its stability with culture Usman, Olalekan H. Zhang, Liting Xie, Gengqiang Kocher, Hemant M. Hwang, Chang-il Wang, Yue Julia Mallory, Xian Irianto, Jerome NPJ Genom Med Article The establishment of patient-derived pancreatic cancer organoid culture in recent years creates an exciting opportunity for researchers to perform a wide range of in vitro studies on a model that closely recapitulates the tumor. One of the outstanding question in pancreatic cancer biology is the causes and consequences of genomic heterogeneity observed in the disease. However, to use pancreatic cancer organoids as a model to study genomic variations, we need to first understand the degree of genomic heterogeneity and its stability within organoids. Here, we used single-cell whole-genome sequencing to investigate the genomic heterogeneity of two independent pancreatic cancer organoid lines, as well as their genomic stability with extended culture. Clonal populations with similar copy number profiles were observed within the organoids, and the proportion of these clones was shifted with extended culture, suggesting the growth advantage of some clones. However, sub-clonal genomic heterogeneity was also observed within each clonal population, indicating the genomic instability of the pancreatic cancer cells themselves. Furthermore, our transcriptomic analysis also revealed a positive correlation between copy number alterations and gene expression regulation, suggesting the “gene dosage” effect of these copy number alterations that translates to gene expression regulation. Nature Publishing Group UK 2022-12-19 /pmc/articles/PMC9763422/ /pubmed/36535941 http://dx.doi.org/10.1038/s41525-022-00342-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Usman, Olalekan H.
Zhang, Liting
Xie, Gengqiang
Kocher, Hemant M.
Hwang, Chang-il
Wang, Yue Julia
Mallory, Xian
Irianto, Jerome
Genomic heterogeneity in pancreatic cancer organoids and its stability with culture
title Genomic heterogeneity in pancreatic cancer organoids and its stability with culture
title_full Genomic heterogeneity in pancreatic cancer organoids and its stability with culture
title_fullStr Genomic heterogeneity in pancreatic cancer organoids and its stability with culture
title_full_unstemmed Genomic heterogeneity in pancreatic cancer organoids and its stability with culture
title_short Genomic heterogeneity in pancreatic cancer organoids and its stability with culture
title_sort genomic heterogeneity in pancreatic cancer organoids and its stability with culture
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763422/
https://www.ncbi.nlm.nih.gov/pubmed/36535941
http://dx.doi.org/10.1038/s41525-022-00342-9
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