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Status: Bibliographieeintrag

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Verfasst von:Dietz, Steffen [VerfasserIn]   i
 Kazdal, Daniel [VerfasserIn]   i
 Harms, Alexander [VerfasserIn]   i
 Endris, Volker [VerfasserIn]   i
 Winter, Hauke [VerfasserIn]   i
 Stenzinger, Albrecht [VerfasserIn]   i
 Warth, Arne [VerfasserIn]   i
 Sill, Martin [VerfasserIn]   i
 Sültmann, Holger [VerfasserIn]   i
Titel:Global DNA methylation reflects spatial heterogeneity and molecular evolution of lung adenocarcinomas
Verf.angabe:Steffen Dietz, Aviezer Lifshitz, Daniel Kazdal, Alexander Harms, Volker Endris, Hauke Winter, Albrecht Stenzinger, Arne Warth, Martin Sill, Amos Tanay and Holger Sültmann
Jahr:2019
Jahr des Originals:2018
Umfang:12 S.
Fussnoten: Online 23 Oct 2018 ; Gesehen am 14.02.2019
Titel Quelle:Enthalten in: International journal of cancer
Ort Quelle:Bognor Regis : Wiley-Liss, 1966
Jahr Quelle:2019
Band/Heft Quelle:144(2019), 5, Seite 1061-1072
ISSN Quelle:1097-0215
Abstract:Lung adenocarcinoma (ADC) is the most prevalent subtype of lung cancer and characterized by considerable morphological and mutational heterogeneity. However, little is known about the epigenomic intratumor variability between spatially separated histological growth patterns of ADC. In order to reconstruct the clonal evolution of histomorphological patterns, we performed global DNA methylation profiling of 27 primary tumor regions, seven matched normal tissues and six lymph node metastases from seven ADC cases. Additionally, we investigated the methylation data from 369 samples of the TCGA ADC cohort. All regions showed varying degrees of methylation changes between segments of different, but also of the same growth patterns. Similarly, copy number variations were seen between spatially distinct segments of each patient. Hierarchical clustering of promoter methylation revealed extensive heterogeneity within and between the cases. Intratumor DNA methylation heterogeneity demonstrated a branched clonal evolution of ADC regions driven by genomic instability with subclonal copy number changes. Notably, methylation profiles within tumors were not more similar to each other than to those from other individuals. In two cases, different tumor regions of the same individuals were represented in distant clusters of the TCGA cohort, illustrating the extensive epigenomic intratumor heterogeneity of ADCs. We found no evidence for the lymph node metastases to be derived from a common growth pattern. Instead, they had evolved early and separately from a particular pattern in each primary tumor. Our results suggest that extensive variation of epigenomic features contributes to the molecular and phenotypic heterogeneity of primary ADCs and lymph node metastases.
DOI:doi:10.1002/ijc.31939
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: http://dx.doi.org/10.1002/ijc.31939
 Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.31939
 DOI: https://doi.org/10.1002/ijc.31939
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:copy number variations
 DNA methylation
 histological growth pattern
 intratumor heterogeneity
 lung adenocarcinoma
K10plus-PPN:1587671832
Verknüpfungen:→ Zeitschrift

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