Whole genome sequencing of colorectal neuroendocrine tumors and in-depth mutational analyses.

Colorectal neuroendocrine tumors (NETs) are rare neoplasms and studies on colorectal NETs are relatively few compared to other tumors. To better understand the pathogenesis of this tumor, we performed whole-genome sequencing and follow-up verification using Sanger sequencing of the colorectal NETs and paired para-tumor tissue. We analyzed the features of the gene mutation spectrum and mutation signature patterns, and analyzed the four pathways that were altered by gene mutation in pancreatic neuroendocrine tumors, including DNA damage and repair, chromatin remodeling, telomere maintenance and mTOR signaling activation. We found that PARP4 which is related to the DNA damage and repair pathway; TSC2, which is related to the mTOR signaling activation pathway; and SLX1A, which is related to telomere maintenance, were mutated in colorectal NETs. Our data analyzed characteristics of gene mutation in colorectal NETs at the whole-genome level, and may help to better understand the pathogenesis of colorectal NETs and may be helpful for potential tumor therapy in the future.