title: High-resolution genomic profiling reveals gain of chromosome 14 as a predictor of poor outcome in ileal carcinoids.
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.
authors.affiliation: Lundberg Laboratory for Cancer Research, Department of Pathology, Sahlgrenska University Hospital, Gula Stråket 8, SE-413 45 Göteborg, Sweden.
authors.forename: Ellinor
authors.initials: E
authors.lastname: Andersson
authors.forename: Christina
authors.initials: C
authors.lastname: Swärd
authors.forename: Göran
authors.initials: G
authors.lastname: Stenman
authors.forename: Håkan
authors.initials: H
authors.lastname: Ahlman
authors.forename: Ola
authors.initials: O
authors.lastname: Nilsson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002276:Carcinoid Tumor / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002869:Chromosome Aberrations; D002883:Chromosomes, Human, Pair 14; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods*; D015894:Genome, Human; D006801:Humans; D007078:Ileal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis