Mutational and copy number asset of primary sporadic neuroendocrine tumors of the small intestine

Michele Simbolo, Caterina Vicentini, Andrea Mafficini, Matteo Fassan, Serena Pedron, Vincenzo Corbo, Luca Mastracci, Borislav Rusev, Corrado Pedrazzani, Luca Landoni, Federica Grillo, Sara Cingarlini, Guido Rindi, Claudio Luchini, Aldo Scarpa, Rita T Lawlor

Research output: Contribution to journalArticlepeer-review


Small intestine neuroendocrine tumors (SI-NETs) represent the most common histotype among small intestine neoplasms, and metastatic disease is usually present at diagnosis. A retrospective series of 52 sporadic primary surgically resected SI-NETs, which were metastatic at diagnosis, was analyzed by high-coverage target sequencing (HCTS) for the mutational status of 57 genes and copy number status of 40 genes selected from recently published genome sequencing data. Seven genes were found to be recurrently mutated: CDKN1B (9.6%), APC and CDKN2C (each 7.7%), BRAF, KRAS, PIK3CA, and TP53 (each 3.8%). Copy number analysis showed frequent allelic loss of 4 genes located on chromosome 18 (BCL2, CDH19, DCC, and SMAD4) in 23/52 (44.2%) and losses on chromosomes 11 (38%) and 16 (15%). Other recurrent copy number variations were gains for genes located on chromosomes 4 (31%), 5 (27%), 14 (36%), and 20 (20%). Univariate survival analysis showed that SRC gene copy number gains were associated with a poorer prognosis (p = 0.047). Recurrent copy number variations are important events in SI-NET and SRC may represent a novel prognostic biomarker for this tumor type.

Original languageEnglish
Pages (from-to)709-717
Number of pages9
JournalVirchows Archiv - A Pathological Anatomy and Histopathology
Issue number6
Publication statusPublished - Dec 2018


  • Adult
  • Aged
  • Biomarkers, Tumor/genetics
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Female
  • Humans
  • Intestinal Neoplasms/genetics
  • Intestine, Small/pathology
  • Male
  • Middle Aged
  • Neuroendocrine Tumors/genetics
  • Prognosis
  • Retrospective Studies


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