ALLELIC DELETIONS ON CHROMOSOME 11Q13 IN MULTIPLE ENDOCRINE NEOPLASIATYPE 1-ASSOCIATED AND SPORADIC GASTRINOMAS AND PANCREATIC ENDOCRINE TUMORS

Endocrine tumors (ETs) of pancreas and duodenum occur sporadically and as a part of multiple endocrine neoplasia type 1 (MEN1). The MEN1 tum or suppressor gene has been localized to chromosome 11q13 by linkage a nalysis but has not yet isolated, Previous allelic deletion studies in enteropancreatic ETs suggested MEN1 gene involvement in tumorigenesis of familial pancreatic ETs (nongastrinomas) and sporadic gastrinomas. However, only a few MEN1-associated duodenal gastrinomas and sporadic pancreatic nongastrinomas have been investigated. We used tissue micr odissection to analyze 95 archival pancreatic and duodenal ETs and met astases from 50 patients for loss of heterozygosity (LOH) on 11q13 wit h 10 polymorphic markers spanning the area of the putative MEN1 gene. Chromosome 11q13 LOH was detected in 23 of 27 (85%) MEN1-associated pa ncreatic ETs (nongastrinomas), 14 of 34 (41%) MEN1-associated gastrino mas, 3 of 16 (19%) sporadic insulinomas, and 8 of 18 (44%) sporadic ga strinomas. Analysis of LOH on 11q13 showed different deletion patterns in ETs from different MEN1 patients and in multiple tumors from indiv idual MEN1 patients, The present results suggest that the MEN1 gene pl ays a role in all four tumor types, The lower rate of 1lq13 LOH in MEN 1-associated and sporadic gastrinomas and sporadic insulinomas as comp ared to MEN1 nongastrinomas may reflect alternative genetic pathways f or the development of these tumors or mechanisms of the MEN1 gene inac tivation that do not involve large deletions, The isolation of the MEN 1 gene is necessary to further define its role in pathogenesis of panc reatic and duodenal ETs.