title: Exome Sequencing and CNV Analysis on Chromosome 18 in Small Intestinal Neuroendocrine Tumors: Ruling Out a Suspect?
abstract: The genetic background in small intestinal neuroendocrine tumors is poorly understood, but several studies have revealed numerical imbalances. Loss of one copy of chromosome 18 is the most frequent genetic aberration in this tumor type, which indirectly suggests that a driver mutation may be present in the remaining allele. The aim of this study was to evaluate the mutation status on chromosome 18 in small intestinal neuroendocrine tumors. DNAs from 7 small intestinal neuroendocrine tumors were subjected to whole exome capture, followed by next generation sequencing and high resolution SNP array followed by copy number variation analysis. Exome capture sequencing generated an average coverage of 50.6-138.2. Only 19 genes were covered less than 8X. No tumor-specific somatic mutation was identified. Genomic profiling revealed loss of chromosome 18 in 5 out of 7 small intestinal neuroendocrine tumors and a number of other aberrancies. Loss of chromosome 18 is the most frequent genetic aberration in small intestinal neuroendocrine tumors, but no evidence for eventual mutations in the remaining allele. This suggests involvement of other mechanisms than point mutations in small intestinal neuroendocrine tumors tumorigenesis.
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Delgado Verdugo
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Crona
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Maharjan
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hellman
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Westin
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Björklund
mesh_terms: D059472:Exome; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology*; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA