Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome with mu
ltiple tumors of the endocrine pancreas, the parathyroid, the pituitary, an
d other tissues. The MEN1 gene at 11q13 is homozygously mutated in the majo
rity of MEN1 tumors. Here we present a genome-wide loss of heterozygosity (
LOH) screening of 23 pancreatic lesions, one duodenal tumor, and one thymic
carcinoid from 13 MEN1 patients. Multiple allelic deletions were found. Fr
actional allelic loss varied from 6-75%, mean 31%. All pancreatic tumors di
splayed LOH on chromosome 11, whereas the frequency of losses for chromosom
es 3, 6, 8, 10, 18, and 21 was over 30%. Different lesions from individual
patients had discrepant patterns of LOH. Intratumoral heterogeneity was rev
ealed, with chromosome 6 and II deletions in most tumor cells, whereas othe
r chromosomal loci were deleted in portions of the analyzed tumor. Chromoso
me 6 deletions were mainly found in lesions from patients with malignant fe
atures. Fractional allelic loss did not correlate to malignancy or to tumor
size. Our findings indicate that MEN1 pancreatic tumors fail to maintain D
NA integrity and demonstrate signs of chromosomal instability.