Analysis of sporadic neuroendocrine tumours of the enteropancreatic system by comparative genomic hybridisation.
BACKGROUND
Chromosomal instability is observed in a wide spectrum of human cancer syndromes. However, to date, little is known of the characteristic genetic changes in sporadic neuroendocrine tumours of the gastroenteropancreatic system.


OBJECTIVE
We have studied copy number aberrations (CNAs) in 26 sporadic neuroendocrine tumours of the enteropancreatic system (12 foregut and 14 midgut tumours) by comparative genomic hybridisation (CGH), allowing simultaneous evaluation of the entire tumour genome.


RESULTS
Nearly all tumours (25/26; that is, 96%) showed chromosomal imbalances, including full chromosomal aneuploidies, losses and gains of chromosome arms, interstitial deletions, and amplifications. Whereas gains of chromosomes 4, 5, and 19 were found in both foregut and midgut tumours, gains of chromosomes 20q (58%), 19 (50%), as well as 17p (50%), and partial losses of chromosomes 1p (42%), 2q (42%), 3p, 4q, and 6q (25% each) were frequently observed only in foregut tumours. In contrast, midgut tumours displayed less CNAs. Gains were detected for chromosomes 17q and 19p (57%). Most frequent losses affected chromosomes 18 (43%) and 9p (21%).


CONCLUSIONS
The results of our CGH analyses revealed new distinct candidate regions in the human genome associated with sporadic neuroendocrine tumours. Some of the genetic alterations were shared by foregut and midgut tumours while others discriminated between the two groups. Thus our results allude to the involvement of identical as well as discriminative genetic loci in tumorigenesis and progression of neuroendocrine neoplasms of the foregut and midgut. Based on these findings potential new candidate genes will be discussed.
Universitätsklinikum Charité der Humboldt-Universität zu Berlin, Campus Virchow-Klinikum, Institut für Humangenetik, Augustenburger Platz 1, D-13353 Berlin, Germany.
H
H
Tönnies
M R
MR
Toliat
C
C
Ramel
U F
UF
Pape
H
H
Neitzel
W
W
Berger
B
B
Wiedenmann
D000293:Adolescent; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D002869:Chromosome Aberrations / Q000235:genetics*; D002872:Chromosome Deletion; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D010190:Pancreatic Neoplasms / Q000235:genetics*