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High-resolution genomic profiling reveals gain of chromosome 14 as a predictor of poor outcome in ileal carcinoids.

Journal article
Authors Ellinor Andersson
Christina Swärd
Göran Stenman
Håkan Ahlman
Ola Nilsson
Published in Endocrine-related cancer
Volume 16
Issue 3
Pages 953-66
ISSN 1479-6821
Publication year 2009
Published at Institute of Clinical Sciences, Department of Surgery
Institute of Biomedicine, Department of Pathology
Pages 953-66
Language en
Links dx.doi.org/10.1677/ERC-09-0052
Keywords Adult, Aged, Aged, 80 and over, Carcinoid Tumor/*diagnosis/*genetics/mortality/pathology, *Chromosome Aberrations, *Chromosomes, Human, Pair 14, Comparative Genomic Hybridization/methods, Female, Gene Dosage, Gene Expression Profiling/*methods, Genome, Human, Humans, Ileal Neoplasms/*diagnosis/*genetics/mortality/pathology, Male, Middle Aged, Prognosis, Recurrence, Survival Analysis
Subject categories Cell and Molecular Biology

Abstract

Ileal carcinoids are malignant neuroendocrine tumours of the small intestine. The aim of this study was to obtain a high-resolution genomic profile of ileal carcinoids in order to define genetic changes important for tumour initiation, progression and survival. Forty-three patients with ileal carcinoids were investigated by high-resolution array-based comparative genomic hybridization. The average number of copy number alterations (CNAs) per tumour was 7.1 (range 1-22), with losses being more common than gains (ratio 1.4). The most frequent CNA was loss of chromosome 18 (74%). Other frequent CNAs were gain of chromosome 4, 5, 14 and 20, and loss of 11q22.1-q22.2, 11q22.3-q23.1 and 11q23.3, and loss of 16q12.2-q22.1 and 16q23.2-qter. Two distinct patterns of CNAs were found; the majority of tumours was characterized by loss of chromosome 18 while a subgroup of tumours had intact chromosome 18, but gain of chromosome 14. Survival analysis, using a series of Poisson regressions including recurrent CNAs, demonstrated that gain of chromosome 14 was a strong predictor of poor survival. In conclusion, high-resolution profiling demonstrated two separate patterns of CNAs in ileal carcinoids. The majority of tumours showed loss of chromosome 18, which most likely represents a primary event in the development and pathogenesis of tumours. A different genetic pathway is operative in a subgroup of tumours; this is characterized by gain of chromosome 14 and is strongly associated with poor prognosis. Predictive fluorescence in situ hybridization analysis of chromosome 14 status in patients with ileal carcinoids is suggested.

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