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

Scientific Reports
Dirk WalterOliver Waidmann

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 exo...Continue Reading

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Citations

Aug 11, 2018·Journal of Oncology Practice·Claire K Mulvey, Emily K Bergsland
Jan 16, 2019·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Yuji EsoHiroshi Seno
Jan 19, 2019·Endocrine Reviews·Andrea Mafficini, Aldo Scarpa
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Feb 27, 2020·Computational and Structural Biotechnology Journal·Kathleen SprouffskeAudrey Kauffmann
Jan 30, 2021·BMC Cancer·Tobias HofvingYvonne Arvidsson

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Datasets Mentioned

BETA
SRP126752

Methods Mentioned

BETA
surgical resection
exome sequencing
biopsy
PCR
Assay
PCRs
Methylation Assay
chip

Software Mentioned

varscan
FuncAssociate
GeneRanker
Burrows Aligner (
SAS
Integrative Genomics Viewer
BWA
SAMtools
- mem
BiAS

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