Deletion of chromosome 1, but not mutation of MEN-1, predicts prognosis in sporadic pancreatic endocrine tumors.
Pancreatic endocrine tumors (PETs) may be sporadic or inherited in the multiple endocrine neoplasia type 1 (MEN-1) syndrome. The inherited form is caused by mutations of the MEN-1 gene, which functions as a tumor suppressor gene and maps to chromosome 11q13. These tumors tend to have a better prognosis than their sporadic counterparts, which often have mutations of the MEN-1 gene. Previous molecular analyses of sporadic PETs suggest a high frequency of loss of heterozygosity (LOH) at chromosome 1 as well as mutation of MEN-1. In this study we correlate abnormalities of MEN-1 and chromosome 1 LOH with the biological behavior of sporadic PETs. Loss of heterozygosity for markers at chromosome 11q13 and mutation of MEN-1 were equally frequent in tumors with or without liver metastases. Mutation of MEN-1 is more frequent in gastrinomas than in non-gastrinomas. Loss of heterozygosity for markers on chromosome 1 is more frequent in PETs with liver metastases. These results suggest a molecular tumor model in which there is a dichotomy in the development of benign and malignant PETs.
Guo
Sydney S
SS
Department of Surgery, West Los Angeles VA Medical Center and the UCLA School of Medicine, Los Angeles, CA 90073, USA.
Wu
Alan Y
AY
Sawicki
Mark P
MP
D007516:Adenoma, Islet Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D018273:Carcinoma, Islet Cell / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D019656:Loss of Heterozygosity; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009154:Mutation; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011518:Proto-Oncogene Proteins
C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins