Figure 3. Integrative analysis of genomic alterations in SI-NET.

SNVs and SCNAs are clustered into pathways of carcinogenesis and tumor maintenance. Canonical concepts and signaling models relevant to molecular carcinogenesis were found to be recurrently altered by nonsynonymous, potentially deleterious somatic SNVs and SCNAs. Chromatin remodeling, mitosis/spindle formation, the DNA damage response, and the regulation of apoptosis are concepts controlling basic mechanisms of cell growth and have established roles in cancer. RAS, ERK/MAPK, and Wnt signaling are classic pathways of cancer. Axon guidance genes have recently been recognized as tumor suppressors (30). PI3K/Akt/mTOR signaling is a mechanism of tumorigenesis. Blue, nonsynonymous exonic point mutation; yellow, splice donor or splice acceptor site mutation; red, amplification; green, deletion.