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Open Access 01-12-2018 | Original Article

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

Authors: 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

Published in: Virchows Archiv | Issue 6/2018

Abstract

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.

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Title: Mutational and copy number asset of primary sporadic neuroendocrine tumors of the small intestine
Authors: 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
Publication date: 01-12-2018
Publisher: Springer Berlin Heidelberg
Published in: Virchows Archiv / Issue 6/2018
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-018-2450-x

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

Abstract

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Abstract

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