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This Article Accepted manuscript (PDF) Supplementary Data All Versions of this Article: ERC-09-0052v1 16/3/953    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Andersson, E. Articles by Nilsson, O. Search for Related Content PubMed PubMed Citation Articles by Andersson, E. Articles by Nilsson, O.

E Andersson, Pathology, Sahlgrenska University Hospital, Goteborg, Sweden
C Swärd, Surgery, Sahlgrenska University Hospital, Goteborg, Sweden
G Stenman, Pathology, Sahlgrenska University Hospital, Goteborg, Sweden
H Ahlman, Surgery, Sahlgrenska University Hospital, Goteborg, Sweden
O Nilsson, Pathology, Sahlgrenska University Hospital, Goteborg, Sweden

Correspondence: Ola Nilsson, Email: ola.nilsson{at}llcr.med.gu.se

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 20, 4, 5, and 14, 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 were 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 FISH analysis of chromosome 14 status in patients with ileal carcinoids is suggested.