scholarly journals Multiple Endocrine Neoplasia Type 1: The Potential Role of microRNAs in the Management of the Syndrome

2020 ◽  
Vol 21 (20) ◽  
pp. 7592
Author(s):  
Simone Donati ◽  
Simone Ciuffi ◽  
Francesca Marini ◽  
Gaia Palmini ◽  
Francesca Miglietta ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Multiple Endocrine Neoplasia ◽  
Potential Role ◽  
Multiple Endocrine Neoplasia Type ◽  
Treatment Options ◽  
Endocrine Tumors ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited tumor syndrome, characterized by the development of multiple neuroendocrine tumors (NETs) in a single patient. Major manifestations include primary hyperparathyroidism, gastro-entero-pancreatic neuroendocrine tumors, and pituitary adenomas. In addition to these main NETs, various combinations of more than 20 endocrine and non-endocrine tumors have been described in MEN1 patients. Despite advances in diagnostic techniques and treatment options, which are generally similar to those of sporadic tumors, patients with MEN1 have a poor life expectancy, and the need for targeted therapies is strongly felt. MEN1 is caused by germline heterozygous inactivating mutations of the MEN1 gene, which encodes menin, a tumor suppressor protein. The lack of a direct genotype–phenotype correlation does not permit the determination of the exact clinical course of the syndrome. One of the possible causes of this lack of association could be ascribed to epigenetic factors, including microRNAs (miRNAs), single-stranded non-coding small RNAs that negatively regulate post-transcriptional gene expression. Some miRNAs, and their deregulation, have been associated with MEN1 tumorigenesis. Recently, an extracellular class of miRNAs has also been identified (c-miRNAs); variations in their levels showed association with various human diseases, including tumors. The aim of this review is to provide a general overview on the involvement of miRNAs in MEN1 tumor development, to be used as possible targets for novel molecular therapies. The potential role of c-miRNAs as future non-invasive diagnostic and prognostic biomarkers of MEN1 will be discussed as well.

scholarly journals Germline MEN1 mutations in sixteen Japanese families with multiple endocrine neoplasia type 1 (MEN1)

1999 ◽  
pp. 475-480 ◽  
Author(s):  
N Hai ◽  
N Aoki ◽  
A Matsuda ◽  
T Mori ◽  
S Kosugi
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Family Members ◽  
Premature Stop Codon ◽  
Germline Mutations ◽  
Endocrine Tumors ◽  
Men1 Gene ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is a syndrome of endocrine tumors involving the parathyroids, anterior pituitary and enteropancreatic neuroendocrine tissues, and is inherited in an autosomal dominant manner. Recently, the gene responsible for this syndrome, MEN1, was positionally cloned in 11q13. We aimed to assess the significance of MEN1 gene diagnostics in families with MEN1. DESIGN: Sixteen probands of familial MEN1 and their 40 family members were subjected to the study. METHODS: Full-length sequencing of the open reading frame and exon-intron boundaries in the MEN1 gene was performed with probands of familial MEN1. Family members were examined for the identified mutation in the proband. RESULTS: We identified heterozygous germline mutations of the MEN1 gene in all of 16 Japanese MEN1 families examined, achieving the highest detectability of MEN1 mutations in familial MEN1 among studies that examined more than 10 families. Eleven kinds of the identified MEN1 germline mutations were novel. More than half were nonsense or frameshift mutations resulting in a premature stop codon (9/15; 60%), and no mutation hot spots or no apparent genotype-phenotype relationships were observed, in support of the results of other studies. We identified 40 mutant MEN1 gene carriers and 16 non-carriers in the course of the present study in those families. CONCLUSIONS: Analysis of the germline mutations in the MEN1 gene, providing significantly useful clinical information to probands and family members of MEN1, should be considered as a standard procedure and categorized as belonging to Group 1 cancer predisposition testing by the American Society of Clinical Oncology.

scholarly journals Surgery for Gastrinoma and Insulinoma in Multiple Endocrine Neoplasia Type 1

2006 ◽  
Vol 4 (2) ◽  
pp. 148-153 ◽  
Author(s):  
Jeffrey A. Norton ◽  
Tony D. Fang ◽  
Robert T. Jensen
Keyword(s):  
Gastric Acid ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Endocrine Tumors ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Pancreatic Endocrine Tumors ◽  
Gastric Acid Hypersecretion ◽  
Acid Hypersecretion

The surgical management of pancreatic endocrine tumors in patients with multiple endocrine neoplasia type 1 remains controversial. Gastrinoma and insulinoma are the 2 most common functional pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. Gastrinomas cause gastric acid hypersecretion and peptic ulcer disease that are best managed using proton pump inhibitors. Surgery to remove the gastrinoma in patients with multiple endocrine neoplasia type 1 is seldom curative unless a more extensive Whipple pancreaticoduodenectomy is performed. Because the prognosis is excellent, aggressive resections such as a Whipple procedure are only indicated for large, locally metastatic, advanced tumors. Furthermore, surgery to remove imageable tumors that are 2 cm in diameter is associated with excellent outcomes and decreased probability of liver metastases. Because gastrinomas are commonly multiple and most originate in the duodenum and develop lymph node metastases, the duodenum should be opened and all tumors and lymph nodes excised. Insulinomas cause hypoglycemia that results in neuroglycopenic symptoms. Medical management of the hypoglycemia is less effective than that of the gastric acid hypersecretion. Fortunately, the insulinoma is usually clearly identified using routine pancreatic imaging studies. There is a high likelihood of cure when the insulinoma is excised surgically. However, recurrent hypoglycemia may occur, and careful follow-up is indicated.

Role of 68Ga-DOTATATE PET/CT in patients with multiple endocrine neoplasia type 1 (MEN1)

Endocrine ◽  
2015 ◽  
Vol 52 (3) ◽  
pp. 488-494 ◽  
Author(s):  
Secondo Lastoria ◽  
Francesca Marciello ◽  
Antongiulio Faggiano ◽  
Luigi Aloj ◽  
Corradina Caracò ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Pet Ct

scholarly journals Clues For Genetic Anticipation In Multiple Endocrine Neoplasia Type 1

2020 ◽  
Vol 105 (7) ◽  
pp. e2491-e2500
Author(s):  
Medard F M van den Broek ◽  
Bernadette P M van Nesselrooij ◽  
Carolina R C Pieterman ◽  
Annemarie A Verrijn Stuart ◽  
Annenienke C van de Ven ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Multiple Endocrine Neoplasia ◽  
Molecular Mechanisms ◽  
Multiple Endocrine Neoplasia Type ◽  
Genetic Anticipation ◽  
Screening Programs ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Successive Generations

Abstract Context Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disease caused by the loss of function of the MEN1 gene, a tumor-suppressor gene that encodes the protein menin. It is characterized by the occurrence of primary hyperparathyroidism (pHPT), duodenopancreatic neuroendocrine tumors (dpNET), pituitary tumors (PIT), adrenal adenomas, and bronchopulmonary (bp-NET), thymic, and gastric neuroendocrine tumors. More insight into factors influencing the age-related penetrance of MEN1 manifestations could provide clues for more personalized screening programs. Objective To investigate whether genetic anticipation plays a role in the largest known MEN1 families in the Netherlands. Methods All Dutch MEN1 families with ≥ 10 affected members in ≥ 2 successive generations were identified. Age at detection of the different MEN1-related manifestations were compared among generations using regression analyses adjusted for competing risks. To correct for the beneficial effect of being under surveillance, manifestations occurring during surveillance were also separately compared. Results A total of 152 MEN1 patients from 10 families were included. A significantly decreased age at detection of pHPT, dpNET, PIT, and bp-NET was found in successive generations (P < 0.0001). Adjusted analyses led to the same results. Conclusions These results suggest the presence of genetic anticipation. However, due to a risk of residual bias, the results must be interpreted with caution. After independent validation in other cohorts and further translational research investigating the molecular mechanisms explaining this phenomenon in MEN1, the results might add to future, more personalized, screening protocols and earlier screening for future generations of MEN1 patients.

scholarly journals Multiple Endocrine Neoplasia Type 1: Latest Insights

2020 ◽  
Author(s):  
Maria Luisa Brandi ◽  
Sunita K Agarwal ◽  
Nancy D Perrier ◽  
Kate E Lines ◽  
Gerlof D Valk ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Genetic Diagnosis ◽  
Diagnostic Tools ◽  
Surgical Approaches ◽  
Endocrine Tumors ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Basic Biology

Abstract Multiple Endocrine Neoplasia Type 1 (MEN1), a rare tumor syndrome that is inherited in an autosomal dominant pattern, is continuing to raise great interest for endocrinology, gastroenterology, surgery, radiology, genetics and molecular biology specialists. There have been two major clinical practice guidance papers that were published in the past two decades, with the most recent publication 8 years ago. Since then, several new insights on the basic biology and clinical features of MEN1 have appeared in the literature and those data are discussed in this review. The genetic and molecular interactions of the MEN1 encoded protein menin with transcription factors and chromatin modifying proteins in cell signaling pathways mediated by TGF-β/BMP, few nuclear receptors, Wnt/β-catenin and Hedgehog (Hh), and preclinical studies in mouse models have facilitated the understanding of the pathogenesis of MEN1-associated tumors and potential pharmacological interventions. The advancements in genetic diagnosis have offered a chance to recognize MEN1 related conditions in germline MEN1 mutation negative patients. There is a rapidly accumulating knowledge about clinical presentation in children, adolescents and pregnancy that is translatable into the management of these very fragile patients. The discoveries about the genetic and molecular signatures of sporadic neuro-endocrine tumors support the development of clinical trials with novel targeted therapies, along with advancements in diagnostic tools and surgical approaches. Finally, quality of life studies in patients affected by MEN1 and related conditions represent an effort necessary to develop a pharmacoeconomic interpretation of the problem. Because advances are being made both broadly and in focused areas, this timely review presents and discusses those studies collectively.

scholarly journals No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

2015 ◽  
Vol 100 (10) ◽  
pp. 3850-3855 ◽  
Author(s):  
Sjoerd Nell ◽  
Rachel S. van Leeuwaarde ◽  
Carolina R. C. Pieterman ◽  
Joanne M. de Laat ◽  
Ad R. Hermus ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Metastatic Disease ◽  
Cumulative Incidence ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Blood Type ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Abo Blood Type

Context: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore, blood type O was proposed as an additional factor to personalize screening criteria for neuroendocrine tumors in MEN1 patients. Objective: The aim of this study was to assess the association between blood type O and the occurrence of neuroendocrine tumors in the national Dutch MEN1 cohort. Design: This is a cohort study using the Dutch National MEN1 database, which includes more than 90% of the Dutch MEN1 population. Demographic and clinical data were analyzed by blood type. Chi-square tests and Fisher exact tests were used to determine the association between blood type O and occurrence of neuroendocrine tumors. A cumulative incidence analysis (Gray's test) was performed to assess the equality of cumulative incidence of neuroendocrine tumors in blood type groups, taking death into account as a competing risk. Results: The ABO blood type of 200 of 322 MEN1 patients was known. Demographic and clinical characteristics were similar among blood type O and non-O type cohorts. The occurrence of neuroendocrine tumors of the lung, thymus, pancreas, and gastrointestinal tract was equally distributed across the blood type O and non-O type cohorts (Grays's test for equality; P = 0.72). Furthermore, we found no association between blood type O and the occurrence of metastatic disease or survival. Conclusions: An association between blood type O and the occurrence of neuroendocrine tumors in MEN1 patients was not confirmed. For this reason, the addition of the blood type to screening and surveillance practice seems not to be of additional value for identifying MEN1 patients at risk for the development of neuroendocrine tumors, metastatic disease, or a shortened survival.

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