TY  - JOUR
A1  - Walter, Dirk Henning
A1  - Harter, Patrick Nikolaus
A1  - Battke, Florian
A1  - Winkelmann, Anne Ria
A1  - Schneider, Markus
A1  - Holzer, Katharina
A1  - Koch, Christine
A1  - Bojunga, Jörg
A1  - Zeuzem, Stefan
A1  - Hansmann, Martin-Leo
A1  - Peveling-Oberhag, Jan Franz-Josef
A1  - Waidmann, Oliver
T1  - Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors
T2  - Scientific reports
N2  - 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.
KW  - DNA methylation
KW  - Endocrine cancer
KW  - Neuroendocrine cancer
KW  - Next-generation sequencing
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46377
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-463778
SN  - 2045-2322
N1  - 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/.
VL  - 8
IS  - 1, Art. 3811
SP  - 1
EP  - 9
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -