Genomic landscape of pancreatic neuroendocrine tumors

Niklas Gebauer*, Christian Schmidt-Werthern, Veronica Bernard, Alfred C. Feller, Tobias Keck, Nehara Begum, Dirk Rades, Hendrik Lehnert, Georg Brabant, Christoph Thorns

*Corresponding author for this work
12 Citations (Scopus)


METHODS: A high-resolution array-based comparative genomic hybridization approach was utilized in order to investigate and quantify chromosomal aberrations in a panel of 37 primary PanNET and 11 metastatic samples. DNA samples were extracted from formalin-fixed and paraffin-embedded tumor specimen. Genomic findings were correlated with histopathological and immunohistochemical data. Moreover, the dataset was subjected to employing an unsupervised hierarchical clustering analysis approach utilizing Euclidean distance and average linkage and associations between genomically defined tumor groups and recurrent CNAs or clinicopathological features of the study group were assessed.

AIM: To investigate the prognostic role of genomic stability and copy number alterations (CNAs) pancreatic neuroendocrine tumors (PanNETs).

RESULTS: Numerous chromosomal aberrations were recurrently detected in both, primary tumor samples and metastases. Copy number gains were most frequently observed at 06p22.2-p22.1 (27.1%), 17p13.1 (20.8%), 07p21.3-p21.2 (18.8%), 09q34.11 (18.8%). Genomic losses were significantly less frequent and the only recurrent aberration affected 08q24.3 (6.3%). Moreover, we detected a high degree of genomic heterogeneity between primary tumors and metastatic lesions. Unsupervised hierarchical clustering of loci affected by CNAs in more than 3 primary tumor samples revealed two genetically distinct tumor groups as well as two chromosomal clusters of genomic imbalances indicating a small subset of tumors with common molecular features (13.5%). Aberrations affecting 6p22.2-22.1, 8q24.3, 9q34.11 and 17p13.1 (P = 0.011; 0.003; 0.003; 0.001), were significantly associated with a poorer survival prognosis.

CONCLUSION: This study suggests that several frequent CNAs in numerous candidate regions are involved in the pathogenesis and metastatic progression of Pan-NET.

Original languageEnglish
JournalWorld Journal of Gastroenterology
Issue number46
Pages (from-to)17498-17506
Number of pages9
Publication statusPublished - 14.12.2014

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)


Dive into the research topics of 'Genomic landscape of pancreatic neuroendocrine tumors'. Together they form a unique fingerprint.

Cite this