Classical midgut carcinoids are rare intestinal neuroendocrine tumors that
often present with metastases at diagnosis. In contrast to foregut carcinoi
ds, midgut carcinoids are not related to the multiple endocrine neoplasia t
ype I syndrome, and the mechanisms involved in their tumorigenesis are unkn
own. Eight classical midgut carcinoids were analyzed by genome-wide screeni
ng for loss of heterozygosity, Deletions on chromosome 18 were found in 88%
of the tumors. DNA sequencing and immunohistochemical staining for Smad4/D
PC4, which often is homozygously mutated in pancreatic and colon carcinomas
, revealed no aberrations. In I tumor, a region telomeric to the Smad4/DPC4
/DCC genes at 18q21 was deleted, Other chromosomes were affected in 3 lesio
ns only. The high frequency of chromosome 18 deletions strongly indicates a
genetic alteration of importance in classical midgut carcinoid tumorigenes
is, apparently not involving the Smad4/DPC4 gene. (C) 2001 Wiley-Liss. Inc.