High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss

Abstract

Carcinoid tumors of the small intestine are characterized by an indolent clinical course, secretion of neuropeptides, and resistance to standard cytotoxic chemotherapy. To evaluate the molecular events underlying carcinoid tumorigenesis, we used high-resolution arrays of single nucleotide polymorphisms to study chromosomal gains and losses in 24 primary and metastatic small bowel carcinoid tumors derived from 18 patients. Regions of gain or loss comprising whole chromosomes or large chromosomal regions constituted the most common class of anomalies. Loss of all or most of chromosome 18 was the commonest finding, evident in 11 of the 18 cases. Heterozygosity was also lost on chromosome arms 9p and 16q. The amplitude of observed gains was modest in comparison to those reported in some other tumor types. One focal region of recurrent gain on 14q mapped to the locus of the gene encoding the antiapoptotic protein DAD1, and immunohistochemical staining confirmed DAD1 protein expression in tumor samples. This detailed study of an uncommon neoplasm provides a basis to investigate putative oncogenes and tumor suppressor genes in intestinal carcinoid tumors.