Comparative genomic hybridization identifies loss of 18q22-qter as an early and specific event in tumorigenesis of midgut carcinoids

Carcinoid tumors are rare neuroendocrine tumors occurring in the lung or in the digestive tract where they are further subclassified as foregut, midgu t, or hindgut carcinoids, To gain a better understanding of the genetic bas is of the different types of carcinoid tumors, we have characterized numeri cal imbalances in a series of midgut carcinoids, and compared the results t o previous findings in carcinoids from the lung. Numerical imbalances were revealed in 16 of the 18 tumors, and the most commonly detected aberrations were losses of 18q22-qter (67%), 11q22-q23 (33%), and 16q21-qter (22%), an d gain of 4p14-qter (22%). The total number of alterations found in the met astases was significantly higher than in the primary tumors, indicating til e accumulation of acquired genetic changes in the tumor progression. Losses of 18q and 11q were present both in primary tumors and metastases, whereas loss of 16q and gain of 4 mere only detected in metastases, Furthermore, t he pattern of comparative genomic hybridization alterations varied dependin g on the total number of detected alterations. Taken together, the findings would suggest a progression of numerical imbalances, in which loss of 18q and 11q represent early events, and loss of 16q and gain of 4p are late eve nts in the tumor progression of midgut carcinoids. When compared to previou sly published comparative genomic hybridization abnormalities in lung carci noids, loss of 11q was found to occur in both tumor types, whereas loss of 18q and 16q and gain of 4 were not revealed in lung carcinoids, The results indicate that inactivation of a putative tumor suppressor gene in 18q22-qt er represents a frequent and early event that is specific for the developme nt of midgut carcinoids.