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DNA methylation intratumor heterogeneity in localized lung adenocarcinomas

Cancers are composed of cells with distinct molecular and phenotypic features within a given tumor, a phenomenon termed intratumor heterogeneity (ITH). Previously, we have demonstrated genomic ITH in localized lung adenocarcinomas; however, the nature of methylation ITH in lung cancers has not been...

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Autores principales: Quek, Kelly, Li, Jun, Estecio, Marcos, Zhang, Jiexin, Fujimoto, Junya, Roarty, Emily, Little, Latasha, Chow, Chi-Wan, Song, Xingzhi, Behrens, Carmen, Chen, Taiping, William, William N., Swisher, Stephen, Heymach, John, Wistuba, Ignacio, Zhang, Jianhua, Futreal, Andrew, Zhang, Jianjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400640/
https://www.ncbi.nlm.nih.gov/pubmed/28423542
http://dx.doi.org/10.18632/oncotarget.15777
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author Quek, Kelly
Li, Jun
Estecio, Marcos
Zhang, Jiexin
Fujimoto, Junya
Roarty, Emily
Little, Latasha
Chow, Chi-Wan
Song, Xingzhi
Behrens, Carmen
Chen, Taiping
William, William N.
Swisher, Stephen
Heymach, John
Wistuba, Ignacio
Zhang, Jianhua
Futreal, Andrew
Zhang, Jianjun
author_facet Quek, Kelly
Li, Jun
Estecio, Marcos
Zhang, Jiexin
Fujimoto, Junya
Roarty, Emily
Little, Latasha
Chow, Chi-Wan
Song, Xingzhi
Behrens, Carmen
Chen, Taiping
William, William N.
Swisher, Stephen
Heymach, John
Wistuba, Ignacio
Zhang, Jianhua
Futreal, Andrew
Zhang, Jianjun
author_sort Quek, Kelly
collection PubMed
description Cancers are composed of cells with distinct molecular and phenotypic features within a given tumor, a phenomenon termed intratumor heterogeneity (ITH). Previously, we have demonstrated genomic ITH in localized lung adenocarcinomas; however, the nature of methylation ITH in lung cancers has not been well investigated. In this study, we generated methylation profiles of 48 spatially separated tumor regions from 11 localized lung adenocarcinomas and their matched normal lung tissues using Illumina Infinium Human Methylation 450K BeadChip array. We observed methylation ITH within the same tumors, but to a much less extent compared to inter-individual heterogeneity. On average, 25% of all differentially methylated probes compared to matched normal lung tissues were shared by all regions from the same tumors. This is in contrast to somatic mutations, of which approximately 77% were shared events amongst all regions of individual tumors, suggesting that while the majority of somatic mutations were early clonal events, the tumor-specific DNA methylation might be associated with later branched evolution of these 11 tumors. Furthermore, our data showed that a higher extent of DNA methylation ITH was associated with larger tumor size (average Euclidean distance of 35.64 (> 3cm, median size) versus 27.24 (<= 3cm), p = 0.014), advanced age (average Euclidean distance of 34.95 (above 65) verse 28.06 (below 65), p = 0.046) and increased risk of postsurgical recurrence (average Euclidean distance of 35.65 (relapsed patients) versus 29.03 (patients without relapsed), p = 0.039).
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spelling pubmed-54006402017-05-03 DNA methylation intratumor heterogeneity in localized lung adenocarcinomas Quek, Kelly Li, Jun Estecio, Marcos Zhang, Jiexin Fujimoto, Junya Roarty, Emily Little, Latasha Chow, Chi-Wan Song, Xingzhi Behrens, Carmen Chen, Taiping William, William N. Swisher, Stephen Heymach, John Wistuba, Ignacio Zhang, Jianhua Futreal, Andrew Zhang, Jianjun Oncotarget Research Paper Cancers are composed of cells with distinct molecular and phenotypic features within a given tumor, a phenomenon termed intratumor heterogeneity (ITH). Previously, we have demonstrated genomic ITH in localized lung adenocarcinomas; however, the nature of methylation ITH in lung cancers has not been well investigated. In this study, we generated methylation profiles of 48 spatially separated tumor regions from 11 localized lung adenocarcinomas and their matched normal lung tissues using Illumina Infinium Human Methylation 450K BeadChip array. We observed methylation ITH within the same tumors, but to a much less extent compared to inter-individual heterogeneity. On average, 25% of all differentially methylated probes compared to matched normal lung tissues were shared by all regions from the same tumors. This is in contrast to somatic mutations, of which approximately 77% were shared events amongst all regions of individual tumors, suggesting that while the majority of somatic mutations were early clonal events, the tumor-specific DNA methylation might be associated with later branched evolution of these 11 tumors. Furthermore, our data showed that a higher extent of DNA methylation ITH was associated with larger tumor size (average Euclidean distance of 35.64 (> 3cm, median size) versus 27.24 (<= 3cm), p = 0.014), advanced age (average Euclidean distance of 34.95 (above 65) verse 28.06 (below 65), p = 0.046) and increased risk of postsurgical recurrence (average Euclidean distance of 35.65 (relapsed patients) versus 29.03 (patients without relapsed), p = 0.039). Impact Journals LLC 2017-02-28 /pmc/articles/PMC5400640/ /pubmed/28423542 http://dx.doi.org/10.18632/oncotarget.15777 Text en Copyright: © 2017 Quek et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Quek, Kelly
Li, Jun
Estecio, Marcos
Zhang, Jiexin
Fujimoto, Junya
Roarty, Emily
Little, Latasha
Chow, Chi-Wan
Song, Xingzhi
Behrens, Carmen
Chen, Taiping
William, William N.
Swisher, Stephen
Heymach, John
Wistuba, Ignacio
Zhang, Jianhua
Futreal, Andrew
Zhang, Jianjun
DNA methylation intratumor heterogeneity in localized lung adenocarcinomas
title DNA methylation intratumor heterogeneity in localized lung adenocarcinomas
title_full DNA methylation intratumor heterogeneity in localized lung adenocarcinomas
title_fullStr DNA methylation intratumor heterogeneity in localized lung adenocarcinomas
title_full_unstemmed DNA methylation intratumor heterogeneity in localized lung adenocarcinomas
title_short DNA methylation intratumor heterogeneity in localized lung adenocarcinomas
title_sort dna methylation intratumor heterogeneity in localized lung adenocarcinomas
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400640/
https://www.ncbi.nlm.nih.gov/pubmed/28423542
http://dx.doi.org/10.18632/oncotarget.15777
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