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

Autor: Simbolo M; ARC-Net Research Centre, University and Hospital Trust of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, Piastra Odontoiatrica (II floor), Verona, Italy.; Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy., Vicentini C; ARC-Net Research Centre, University and Hospital Trust of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, Piastra Odontoiatrica (II floor), Verona, Italy.; Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy., Mafficini A; ARC-Net Research Centre, University and Hospital Trust of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, Piastra Odontoiatrica (II floor), Verona, Italy., Fassan M; ARC-Net Research Centre, University and Hospital Trust of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, Piastra Odontoiatrica (II floor), Verona, Italy.; Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Italy., Pedron S; Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy., Corbo V; ARC-Net Research Centre, University and Hospital Trust of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, Piastra Odontoiatrica (II floor), Verona, Italy.; Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy., Mastracci L; Department of Surgical and Diagnostic Sciences (DISC), University of Genoa and IRCCS S. Martino-IST University Hospital, Genoa, Italy., Rusev B; ARC-Net Research Centre, University and Hospital Trust of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, Piastra Odontoiatrica (II floor), Verona, Italy.; Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy., Pedrazzani C; Department of Surgery, General and Hepatobiliary Surgery, University and Hospital Trust of Verona, Verona, Italy., Landoni L; Department of Surgery and Oncology, Unit of Surgery B, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy., Grillo F; Department of Surgical and Diagnostic Sciences (DISC), University of Genoa and IRCCS S. Martino-IST University Hospital, Genoa, Italy., Cingarlini S; Department of Medicine, Section of Medical Oncology, University and Hospital Trust of Verona, Verona, Italy., Rindi G; Intitute of Pathology, Università Cattolica-IRCCS Fondazione Policlinico A. Gemelli, Rome, Italy., Luchini C; Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy., Scarpa A; ARC-Net Research Centre, University and Hospital Trust of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, Piastra Odontoiatrica (II floor), Verona, Italy. aldo.scarpa@univr.it.; Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy. aldo.scarpa@univr.it., Lawlor RT; ARC-Net Research Centre, University and Hospital Trust of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, Piastra Odontoiatrica (II floor), Verona, Italy.; Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy.
Jazyk: angličtina
Zdroj: Virchows Archiv : an international journal of pathology [Virchows Arch] 2018 Dec; Vol. 473 (6), pp. 709-717. Date of Electronic Publication: 2018 Sep 16.
DOI: 10.1007/s00428-018-2450-x
Abstrakt: 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.
Databáze: MEDLINE
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