Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors

Abstract Data on intratumoral heterogeneity of small intestine neuroendocrine tumors (SI-NETs) and related liver metastasis are limited. The aim of this study was to characterize genetic heterogeneity of 5 patients with SI-NETs. Therefore, formalin-fixed, paraffin-embedded tissue samples of primary...

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Autores principales:	Dirk Walter, Patrick N. Harter, Florian Battke, Ria Winkelmann, Markus Schneider, Katharina Holzer, Christine Koch, Jörg Bojunga, Stefan Zeuzem, Martin Leo Hansmann, Jan Peveling-Oberhag, Oliver Waidmann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b786fcb5b9e245fe84cd2828f5a059bc
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spelling	oai:doaj.org-article:b786fcb5b9e245fe84cd2828f5a059bc2021-12-02T15:08:42ZGenetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors10.1038/s41598-018-22115-02045-2322https://doaj.org/article/b786fcb5b9e245fe84cd2828f5a059bc2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-22115-0https://doaj.org/toc/2045-2322Abstract Data on intratumoral heterogeneity of small intestine neuroendocrine tumors (SI-NETs) and related liver metastasis are limited. The aim of this study was to characterize genetic heterogeneity of 5 patients with SI-NETs. Therefore, formalin-fixed, paraffin-embedded tissue samples of primary and metastatic lesions as well as benign liver of five patients with synchronously metastasized, well differentiated SI-NETs were analyzed with whole exome sequencing. For one patient, chip based 850k whole DNA methylome analysis was performed of primary and metastatic tumor tissue as well as control tissue. Thereby, 156 single nucleotide variants (SNVs) in 150 genes were identified and amount of mutations per sample ranged from 9–34 (mean 22). The degree of common (0–94%) and private mutations per sample was strongly varying (6–100%). In all patients, copy number variations (CNV) were found and the degree of intratumoral heterogeneity of CNVs corresponded to SNV analysis. DNA methylation analysis of a patient without common SNVs revealed a large overlap of common methylated CpG sites. In conclusion, SI-NET primary and metastatic lesions show a highly varying degree of intratumoral heterogeneity. Driver events might not be detectable with exome analysis only, and further comprehensive studies including whole genome and epigenetic analyses are warranted.Dirk WalterPatrick N. HarterFlorian BattkeRia WinkelmannMarkus SchneiderKatharina HolzerChristine KochJörg BojungaStefan ZeuzemMartin Leo HansmannJan Peveling-OberhagOliver WaidmannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dirk Walter Patrick N. Harter Florian Battke Ria Winkelmann Markus Schneider Katharina Holzer Christine Koch Jörg Bojunga Stefan Zeuzem Martin Leo Hansmann Jan Peveling-Oberhag Oliver Waidmann Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors
description	Abstract Data on intratumoral heterogeneity of small intestine neuroendocrine tumors (SI-NETs) and related liver metastasis are limited. The aim of this study was to characterize genetic heterogeneity of 5 patients with SI-NETs. Therefore, formalin-fixed, paraffin-embedded tissue samples of primary and metastatic lesions as well as benign liver of five patients with synchronously metastasized, well differentiated SI-NETs were analyzed with whole exome sequencing. For one patient, chip based 850k whole DNA methylome analysis was performed of primary and metastatic tumor tissue as well as control tissue. Thereby, 156 single nucleotide variants (SNVs) in 150 genes were identified and amount of mutations per sample ranged from 9–34 (mean 22). The degree of common (0–94%) and private mutations per sample was strongly varying (6–100%). In all patients, copy number variations (CNV) were found and the degree of intratumoral heterogeneity of CNVs corresponded to SNV analysis. DNA methylation analysis of a patient without common SNVs revealed a large overlap of common methylated CpG sites. In conclusion, SI-NET primary and metastatic lesions show a highly varying degree of intratumoral heterogeneity. Driver events might not be detectable with exome analysis only, and further comprehensive studies including whole genome and epigenetic analyses are warranted.
format	article
author	Dirk Walter Patrick N. Harter Florian Battke Ria Winkelmann Markus Schneider Katharina Holzer Christine Koch Jörg Bojunga Stefan Zeuzem Martin Leo Hansmann Jan Peveling-Oberhag Oliver Waidmann
author_facet	Dirk Walter Patrick N. Harter Florian Battke Ria Winkelmann Markus Schneider Katharina Holzer Christine Koch Jörg Bojunga Stefan Zeuzem Martin Leo Hansmann Jan Peveling-Oberhag Oliver Waidmann
author_sort	Dirk Walter
title	Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors
title_short	Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors
title_full	Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors
title_fullStr	Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors
title_full_unstemmed	Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors
title_sort	genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/b786fcb5b9e245fe84cd2828f5a059bc
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_version_	1718388083011878912

Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors

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