Multiple allelic deletions and intratumoral genetic heterogeneity in MEN1 pancreatic tumors

Citation
O. Hessman et al., Multiple allelic deletions and intratumoral genetic heterogeneity in MEN1 pancreatic tumors, J CLIN END, 86(3), 2001, pp. 1355-1361
Citations number
26
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN journal
0021972X → ACNP
Volume
86
Issue
3
Year of publication
2001
Pages
1355 - 1361
Database
ISI
SICI code
0021-972X(200103)86:3<1355:MADAIG>2.0.ZU;2-Q
Abstract
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.