Genomic landscape of pancreatic neuroendocrine tumors

Pancreatic NETs are increasing in incidence and understanding the genetic mechanisms involved in tumour development is poorly understood. In this study the authors aimed to determine the degree of genomic stability and copy number alterations (CNA) within the group of PanNETs, applying a high resolution array-based comparative genomic hybridization (a-CGH) approach to a panel of 37 primary PanNETs. The second major aim was to assess chromosomal aberrations comparatively between pancreatic primary tumors and metastases (n = 11), in order to identify intra-individual genomic imbalances of potential therapeutic relevance.

They identified a number of chromosomal aberrations that 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, there was a large 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%). Alterations in 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.

This study suggests that several frequent CNAs in numerous candidate regions are involved in the pathogenesis and metastatic progression of PanNET.

Source: World Journal of Gastroenterology