Journal of Clinical Endocrinology & Metabolism, Vol 81, 3164-3167, Copyright © 1996 by Endocrine Society

ARTICLES

Carcinoid tumors frequently display genetic abnormalities involving chromosome 11

O Jakobovitz, D Nass, L DeMarco, AJ Barbosa, FB Simoni, G Rechavi and E Friedman
Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer, Israel.

Carcinoid tumors are neuroendocrine neoplasms that are encountered either sporadically or as part of a familial syndrome, most notably- multiple endocrine neoplasia type 1 (MEN1). The MEN1 gene localizes to chromosome 11 (11q13) and presumably functions as a tumor suppressor gene. The molecular mechanisms underlying carcinoid tumor development and their clonal composition remain largely unknown. To establish whether carcinoid tumors develop via a mechanism similar to other MEN1- associated tumors, and indirectly determine their clonal composition, we analyzed 36 sporadically occurring carcinoid tumors with 16 chromosome 11 microsatellite markers, mostly from around the MEN1 region for loss of heterozygosity (LOH). Twenty one tumors (58%) displayed LOH of at least three markers, five lost almost an entire allele and the rest displayed a discontinuous pattern. Similar, but less extensive analysis was also carried out for 10 additional carcinoid tumors from Brazil, 6 of the 10 showed LOH with at least one marker. Overall, 36 of 46 tumors (78%) displayed LOH. In addition, 20 of 46 (43%) tumors exhibited a pattern of genomic instability. Thus, the majority of sporadically occurring carcinoid tumors are monoclonal whose tumorigenesis involves inactivation of a tumor suppressor gene on chromosome 11 and DNA mismatch repair genes mutations.

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