Chromosomal aberrations are less frequent in ileal carcinoids compared to PNET. Loss on chromosomes 9, 16, and 18. Gain on chromosomes 4, 14, 17, and 20.
Candidate genes for targeted therapy in regions of chromosomal gains include ERBB2 (HER2)
Most frequently occurring chromosomal aberrations comprise large chromosomal regions or whole chromosomes. Loss on chromosomes 9, 16, and 18. Gain on chromosomes 4, 5, 7, and 14. Hierarchical clustering revealed two groups of tumors, a smaller group with clustered gains on chromosomes 4, 5, 7 and 14 and a larger group without clustered gains.
Candidate genes for targeted therapy in regions of chromosomal gains include DAD1, OR4A5, and PRKCA
Loss on chromosomes 9, 11, 13, 16 and 18. Loss of chromosome 18 is the most frequent aberration and an early event in tumorigenesis. Gain on chromosomes 4, 5, 14, and 20. Gain of chromosome 14 is associated with short survival. Ileal carcinoids are separated in two groups: tumors with loss on chromosome 18, and tumors with intact chromosome 18 but gain of chromosome 14.
Familial and sporadic tumors have similar chromosomal aberrations. Loss of chromosome 18 is the most frequent alteration occurring early in tumorigenesis. Minimal regions of deletions are 18q21.1-q21.31, 18q22.1-q22.2, and 18q22.3-q23. Gain on chromosome 7 occurred only in metastasis and correlated solid growth pattern.
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For genes and proteins in bold, therapeutic agents are available for preclinical or clinical testing. BAC: bacterial artificial chromosome; CGH: comparative genomic hybridisation; PNET: pancreatic neuroendocrine tumor; SNP: single-nucleotide polymorphism; WDNC: well-differentiated neuroendocrine carcinoma.
