CARCINOID-TUMORS FREQUENTLY DISPLAY GENETIC ABNORMALITIES INVOLVING CHROMOSOME-11

Carcinoid tumors are neuroendocrine neoplasms that are encountered eit her sporadically or as part of a familial syndrome, most notably - mul tiple endocrine neoplasia type 1 (MEN1). The MEN1 gene localizes to ch romosome 11 (11q13) and presumably functions as a tumor suppressor gen e. 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-associ ated tumors, and indirectly determine their clonal composition, we ana lyzed 36 sporadically occurring carcinoid tumors with 16 chromosome 11 microsatellite markers, mostly from around the MEN1 region for loss o f heterozygosity (LOH). Twenty one tumors (58%) displayed LOH of at le ast three markers, five lost almost an entire allele and the rest disp layed a discontinuous pattern. Similar, but less extensive analysis wa s also carried out for 10 additional carcinoid tumors from Brazil, 6 o f 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 p attern of genomic instability. Thus, the majority of sporadically occu rring carcinoid tumors are monoclonal whose tumorigenesis involves ina ctivation of a tumor suppressor gene on chromosome 11 and DNA mismatch repair genes mutations.