ABSTRACT
Whether early surgical treatment of non-functioning pancreas islet cell tumor (NFPT) provides a favorable quality of life and life expectancy in patients with multiple endocrine neoplasia type 1 (MEN1) remains controversial. We analyzed the long-term clinical courses and surgical outcomes of 14 Japanese patients with MEN1-associated NFPTs. NFPTs smaller than 20 mm in diameter did not show any apparent growth over a long monitoring period. Furthermore, these small NFPTs did not metastasize to regional lymph nodes or the liver. On the other hand, the development of additional NFPTs or metastasis was found in five of six patients with large (35 mm or larger) NFPTs. Among the seven patients who underwent a partial pancreatectomy, six patients developed impaired glucose tolerance or diabetes. The accumulation of more prospective data is needed to clarify the optimal surgical indications for patients with NFPTs, especially among the Japanese population, which has a relatively low insulin secretion potency compared with non-Hispanic white and African-American populations.
Subject(s)
Adenoma, Islet Cell/etiology , Adenoma, Islet Cell/surgery , Multiple Endocrine Neoplasia Type 1/complications , Pancreatic Neoplasms/etiology , Pancreatic Neoplasms/surgery , Adenoma, Islet Cell/diagnostic imaging , Adenoma, Islet Cell/physiopathology , Adult , Asian People , Diabetes Mellitus/etiology , Disease Progression , Female , Follow-Up Studies , Glucose Intolerance/etiology , Humans , Male , Middle Aged , Multiple Endocrine Neoplasia Type 1/ethnology , Neoplasm Metastasis , Neoplasms, Second Primary/diagnostic imaging , Pancreas/physiopathology , Pancreatectomy/adverse effects , Pancreatectomy/methods , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/physiopathology , Tomography, X-Ray ComputedABSTRACT
Multiple endocrine neoplasia type 1 (MEN 1) is characterised by the combination of tumours of the parathyroid, endocrine pancreas and anterior pituitary glands. In 1988 the MEN 1 gene was mapped to chromosome 11q13 and it was cloned in 1997. This gene contains 10 exons and extends across 9 Kb of genomic DNA; it encodes for a product of 610 amino acid named menin whose function is unknown. We have studied 10 unrelated MEN 1 kindreds by a complete sequencing analysis of the entire gene; mutations were identified in nine of them: five deletions, one insertion, two nonsense mutation and a complex alteration consisting of a deletion and an insertion that can be explained by a hairpin loop model. Two of the mutations have been previously described; the other seven were novel, and they were scattered throughout the coding sequence of the gene. As in previous series, no correlation was found between phenotype and genotype.
Subject(s)
Multiple Endocrine Neoplasia Type 1/genetics , Base Sequence , Chromosome Mapping , Chromosomes, Human, Pair 11 , DNA/chemistry , DNA/genetics , Germ-Line Mutation , Humans , Molecular Sequence Data , Multiple Endocrine Neoplasia Type 1/ethnology , Nucleic Acid Conformation , SpainABSTRACT
Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disease characterized by neoplasia of the parathyroid glands, anterior pituitary and endocrine pancreas, is rarely reported in Asian populations. The MEN1 gene, mapped to chromosome 11q13 but yet to be cloned, has been found to be homogeneous in Caucasian populations through linkage analysis. Here, two previously unreported Asian kindreds with MEN1 are described; linkage analysis using microsatellite polymorphic markers in the MEN1 region was carried out. The first kindred, of Mongolian-Chinese origin, is a multigeneration family with over 150 living members, eight of whom are affected to date. The second kindred is of Chinese origin consisting of four affected members. Linkage to chromosome 11q13 was confirmed in both kindreds, supporting evidence for genetic homogeneity. A recombination in the larger kindred localizes the gene distal to marker D11S956, consistent with its placement from previous studies. We also show that it is feasible to use these markers for predictive testing, as four gene carriers were detected in 13 family members with unknown disease status in the first kindred.
