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Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma

Intratumor heterogeneity (ITH) of genomic alterations may impact prognosis of lung adenocarcinoma (LUAD). Here, we investigate ITH of somatic copy number alterations (SCNAs), DNA methylation, and point mutations in lung cancer driver genes in 292 tumor samples from 84 patients with LUAD. LUAD sample...

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Autores principales: Hua, Xing, Zhao, Wei, Pesatori, Angela C., Consonni, Dario, Caporaso, Neil E., Zhang, Tongwu, Zhu, Bin, Wang, Mingyi, Jones, Kristine, Hicks, Belynda, Song, Lei, Sampson, Joshua, Wedge, David C., Shi, Jianxin, Landi, Maria Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235245/
https://www.ncbi.nlm.nih.gov/pubmed/32424208
http://dx.doi.org/10.1038/s41467-020-16295-5
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author Hua, Xing
Zhao, Wei
Pesatori, Angela C.
Consonni, Dario
Caporaso, Neil E.
Zhang, Tongwu
Zhu, Bin
Wang, Mingyi
Jones, Kristine
Hicks, Belynda
Song, Lei
Sampson, Joshua
Wedge, David C.
Shi, Jianxin
Landi, Maria Teresa
author_facet Hua, Xing
Zhao, Wei
Pesatori, Angela C.
Consonni, Dario
Caporaso, Neil E.
Zhang, Tongwu
Zhu, Bin
Wang, Mingyi
Jones, Kristine
Hicks, Belynda
Song, Lei
Sampson, Joshua
Wedge, David C.
Shi, Jianxin
Landi, Maria Teresa
author_sort Hua, Xing
collection PubMed
description Intratumor heterogeneity (ITH) of genomic alterations may impact prognosis of lung adenocarcinoma (LUAD). Here, we investigate ITH of somatic copy number alterations (SCNAs), DNA methylation, and point mutations in lung cancer driver genes in 292 tumor samples from 84 patients with LUAD. LUAD samples show substantial SCNA and methylation ITH, and clonal architecture analyses present congruent evolutionary trajectories for SCNAs and DNA methylation aberrations. Methylation ITH mapping to gene promoter areas or tumor suppressor genes is low. Moreover, ITH composed of genetic and epigenetic mechanisms altering the same cancer driver genes is shown in several tumors. To quantify ITH for valid statistical association analyses, we develope an average pairwise ITH index (APITH), which does not depend on the number of samples per tumor. Both APITH indexes for SCNAs and methylation aberrations show significant associations with poor prognosis. This study further establishes the important clinical implications of genetic and epigenetic ITH in LUAD.
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spelling pubmed-72352452020-05-20 Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma Hua, Xing Zhao, Wei Pesatori, Angela C. Consonni, Dario Caporaso, Neil E. Zhang, Tongwu Zhu, Bin Wang, Mingyi Jones, Kristine Hicks, Belynda Song, Lei Sampson, Joshua Wedge, David C. Shi, Jianxin Landi, Maria Teresa Nat Commun Article Intratumor heterogeneity (ITH) of genomic alterations may impact prognosis of lung adenocarcinoma (LUAD). Here, we investigate ITH of somatic copy number alterations (SCNAs), DNA methylation, and point mutations in lung cancer driver genes in 292 tumor samples from 84 patients with LUAD. LUAD samples show substantial SCNA and methylation ITH, and clonal architecture analyses present congruent evolutionary trajectories for SCNAs and DNA methylation aberrations. Methylation ITH mapping to gene promoter areas or tumor suppressor genes is low. Moreover, ITH composed of genetic and epigenetic mechanisms altering the same cancer driver genes is shown in several tumors. To quantify ITH for valid statistical association analyses, we develope an average pairwise ITH index (APITH), which does not depend on the number of samples per tumor. Both APITH indexes for SCNAs and methylation aberrations show significant associations with poor prognosis. This study further establishes the important clinical implications of genetic and epigenetic ITH in LUAD. Nature Publishing Group UK 2020-05-18 /pmc/articles/PMC7235245/ /pubmed/32424208 http://dx.doi.org/10.1038/s41467-020-16295-5 Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020 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/.
spellingShingle Article
Hua, Xing
Zhao, Wei
Pesatori, Angela C.
Consonni, Dario
Caporaso, Neil E.
Zhang, Tongwu
Zhu, Bin
Wang, Mingyi
Jones, Kristine
Hicks, Belynda
Song, Lei
Sampson, Joshua
Wedge, David C.
Shi, Jianxin
Landi, Maria Teresa
Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma
title Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma
title_full Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma
title_fullStr Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma
title_full_unstemmed Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma
title_short Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma
title_sort genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235245/
https://www.ncbi.nlm.nih.gov/pubmed/32424208
http://dx.doi.org/10.1038/s41467-020-16295-5
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