Home  About us  Contact
 

MEN1 Germline Mutation (men1 + germline_mutation)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Multiple endocrine neoplasia type 1-associated cystic pancreatic endocrine neoplasia and multifocal cholesterol granulomas

PATHOLOGY INTERNATIONAL, Issue 4 2010
Noriko Kimura
A novel combination of tumors was found in a 68 year-old female with Multiple Endocrine Neoplasia type-1 (MEN 1) that included a cystic pancreatic endocrine neoplasm (CPEN), a pituitary adenoma, and multifocal cholesterol granulomas (MCGs) in the breast, pleura, and the extremities. The pancreatic tumor displayed a single central locule surrounded by a thin rim of neoplastic parenchyma. The tumor showed heterogeneity in the architecture that included glandular, trabecular and solid patterns. The tumor cells of the pancreas were immunohistochemically positive for both endocrine and pancreatic acinar markers including chromogranin A, synaptophysin, glucagon, lipase, and reg protein. Electron microscopy revealed that there were numerous smaller dense-cored neurosecretory granules, larger zymogen-like granules and microvilli on the apical side of the tumor cells. The pancreatic tumor was diagnosed as CPEN with acinar cell features. Analysis of the DNA extracted from the tissues revealed that there is a MEN1 germline mutation in exon 10 codon 527, and somatic mutation in exon 2 codon 32 in the pancreatic tumor, and one base pair deletion in exon 2 codon 79 in the pituitary adenoma. Here, we report the case and discuss possible pathogenesis of CPEN and MCGs in a patient with MEN 1. [source]

Age-related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers

CLINICAL ENDOCRINOLOGY, Issue 4 2007
Andreas Machens
Summary Objective, In multiple endocrine neoplasia type 1 (MEN1), age-related tumour penetrance according to the type of MEN1 germline mutation has not been investigated in-depth. This study was conducted to examine whether carriers of out-of-frame/truncating and in-frame MEN1 mutations differ in age-related tumour penetrance. Design, A multicentre study with biochemical, hormonal and radiological screening for MEN1-associated tumours. Patients, A total of 258 MEN1 carriers from six major German tertiary referral centres averaging 43 years of age at last follow-up. Measurements, Main outcome measure was time to first diagnosis of MEN1-associated tumours. Results, Independent of the year of birth and observation period, time to first tumour diagnosis did not vary much by the type of MEN1 germline mutation or endocrine organ system, and perhaps not even by the type of endocrine tumour when the amount of time was considered by which the diagnosis probably has been advanced through the manifestation of hormonal symptoms. Parathyroid hyperplasia and adenomas developed almost twice as often as enteropancreatic and pituitary tumours (77%vs. 49,32%), and more than five to sevenfold as often as adrenal cortical tumours and carcinoids (77%vs. 15,10%), reaching penetrance rates of up to 90%, 60%, 40%, 26% and 17%, respectively. The heterogeneity of tumour penetrance was marked, ranging from 9 years to 25 years for the earliest, and from 68 years to 77 years for the latest tumour manifestation. Conclusions, Because of our inability of predicting tumour penetrance and malignant transformation individually, life-long follow-up of MEN1 carriers is warranted to prevent tumour morbidity. [source]

Novel MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1

CLINICAL ENDOCRINOLOGY, Issue 3 2007
Rodrigo A. Toledo
Summary Objective, To characterize clinical features and identify MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1 (MEN1). Settings, Non-profit academic centre. Patients, Fourteen Brazilian families with MEN1 and 141 at-risk relatives. Results, We identified 12 different MEN1 disease-causing mutations, seven of them previously unreported: 308delC; 375del21; 549A>T (I147F); 1243delA; 1348T>G (L413R); 1351T>C (L414P) and 1523G>T (W471C). Families with the recurrent mutations 360delTCTA and L413R were shown to be unrelated by mitochondrial-DNA and Y-chromosome haplotype analyses. Most of the MEN1 single point mutations involved evolutionarily conserved residues, whereas most of the deletion/frameshift changes occurred in GC-rich repetitive regions. Genetic screening of 141 at-risk family members identified 38 MEN1 mutation carriers, 37 (97·4%) of whom had at least one major MEN1-related tumour upon clinical investigation. Conclusions, High frequencies of MEN1 gene mutations were detected in Brazilian families with MEN1, including seven new genetic mutations that are predicted to cause inactivation of the MEN1 tumour suppressor gene. Our data underscore the need to implement a systematic MEN1 screening programme in Brazil. [source]