Management impact: effects on quality of life and prognosis in MEN1
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant endocrine tumor syndrome, caused by inactivating mutations of the MEN1 tumor suppressor gene at 11q13 locus, which predisposes to develop tumors in target neuroendocrine tissues. As the positional cloning and identification of the causative gene in 1997, genetic diagnosis, by the sequencing-based research of gene mutations, has become an important tool in the early and differential diagnosis of the disease. Application of the genetic test, in MEN1 index cases and in first-degree relatives of mutated patients, has been constantly increasing during the last ...
Source: Endocrine-Related Cancer - September 12, 2017 Category: Endocrinology Authors: Marini, F., Giusti, F., Tonelli, F., Brandi, M. L. Tags: Thematic Review Source Type: research
The future: diagnostic and imaging advances in MEN1 therapeutic approaches and management strategies
Prospective randomized data are lacking, but current clinical expert guidelines recommend annual screening examinations, including laboratory assessments and various imaging modalities (e.g. CT, MRI, scintigraphy and EUS) for patients with multiple endocrine neoplasia type 1 (MEN1). Routine screening is proposed to detect and localize neuroendocrine manifestations as early as possible. The goal is timely intervention to improve quality of life and to increase life expectancy by preventing the development of life-threatening hormonal syndromes and/or metastatic disease. In recent years, some studies compared different and n...
Source: Endocrine-Related Cancer - September 12, 2017 Category: Endocrinology Authors: Manoharan, J., Albers, M. B., Bartsch, D. K. Tags: Thematic Review Source Type: research
MEN4 and CDKN1B mutations: the latest of the MEN syndromes
Multiple endocrine neoplasia (MEN) refers to a group of autosomal dominant disorders with generally high penetrance that lead to the development of a wide spectrum of endocrine and non-endocrine manifestations. The most frequent among these conditions is MEN type 1 (MEN1), which is caused by germline heterozygous loss-of-function mutations in the tumor suppressor gene MEN1. MEN1 is characterized by primary hyperparathyroidism (PHPT) and functional or nonfunctional pancreatic neuroendocrine tumors and pituitary adenomas. Approximately 10% of patients with familial or sporadic MEN1-like phenotype do not have MEN1 mutations o...
Source: Endocrine-Related Cancer - September 12, 2017 Category: Endocrinology Authors: Alrezk, R., Hannah-Shmouni, F., Stratakis, C. A. Tags: Thematic Review Source Type: research
The future: medical advances in MEN1 therapeutic approaches and management strategies
Multiple endocrine neoplasia type 1 is a rare autosomal inherited disorder associated with a high risk for patients to simultaneously develop tumors of the parathyroid glands, duodenopancreatic neuroendocrine tumors and tumors of the anterior pituitary gland. Early identification of MEN1 in patients enables presymptomatic screening of manifestations, which makes timely interventions possible with the intention to prevent morbidity and mortality. Causes of death nowadays have shifted toward local or metastatic progression of malignant neuroendocrine tumors. In early cohorts, complications like peptic ulcers in gastrinoma, r...
Source: Endocrine-Related Cancer - September 12, 2017 Category: Endocrinology Authors: van Leeuwaarde, R. S., de Laat, J. M., Pieterman, C. R. C., Dreijerink, K., Vriens, M. R., Valk, G. D. Tags: Thematic Review Source Type: research
Animal models of MEN1
Animal models of cancer have been instrumental in advancing our understanding of the biology of tumor initiation and progression, in studying gene function and in performing preclinical studies aimed at testing novel therapies. Several animal models of the MEN1 syndrome have been generated in different organisms by introducing loss-of-function mutations in the orthologues of the human MEN1 gene. In this review, we will discuss MEN1 and MEN1-like models in Drosophila, mice and rats. These model systems with their specific advantages and limitations have contributed to elucidate the function of Menin in tumorigenesis, which ...
Source: Endocrine-Related Cancer - September 12, 2017 Category: Endocrinology Authors: Mohr, H., Pellegata, N. S. Tags: Thematic Review Source Type: research
Epigenetic regulation by the menin pathway
There is a trend of increasing prevalence of neuroendocrine tumors (NETs), and the inherited multiple endocrine neoplasia type 1 (MEN1) syndrome serves as a genetic model to investigate how NETs develop and the underlying mechanisms. Menin, encoded by the MEN1 gene, at least partly acts as a scaffold protein by interacting with multiple partners to regulate cellular homeostasis of various endocrine organs. Menin has multiple functions including regulation of several important signaling pathways by controlling gene transcription. Here, we focus on reviewing the recent progress in elucidating the key biochemical role of meni...
Source: Endocrine-Related Cancer - September 12, 2017 Category: Endocrinology Authors: Feng, Z., Ma, J., Hua, X. Tags: Thematic Review Source Type: research
Twenty years of menin: emerging opportunities for restoration of transcriptional regulation in MEN1
Since the discovery of the multiple endocrine neoplasia type 1 (MEN1) gene in 1997, elucidation of the molecular function of its protein product, menin, has been a challenge. Biochemical, proteomics, genetics and genomics approaches have identified various potential roles, which converge on gene expression regulation. The most consistent findings show that menin connects transcription factors and chromatin-modifying enzymes, in particular, the histone H3K4 methyltransferase complexes MLL1 and MLL2. Chromatin immunoprecipitation combined with next-generation sequencing has enabled studying genome-wide dynamics of chromatin ...
Source: Endocrine-Related Cancer - September 12, 2017 Category: Endocrinology Authors: Dreijerink, K. M. A., Timmers, H. T. M., Brown, M. Tags: Thematic Review Source Type: research
The future: genetics advances in MEN1 therapeutic approaches and management strategies
The identification of the multiple endocrine neoplasia type 1 (MEN1) gene in 1997 has shown that germline heterozygous mutations in the MEN1 gene located on chromosome 11q13 predisposes to the development of tumors in the MEN1 syndrome. Tumor development occurs upon loss of the remaining normal copy of the MEN1 gene in MEN1-target tissues. Therefore, MEN1 is a classic tumor suppressor gene in the context of MEN1. This tumor suppressor role of the protein encoded by the MEN1 gene, menin, holds true in mouse models with germline heterozygous Men1 loss, wherein MEN1-associated tumors develop in adult mice after spontaneous lo...
Source: Endocrine-Related Cancer - September 12, 2017 Category: Endocrinology Authors: Agarwal, S. K. Tags: Thematic Review Source Type: research
Happy 20th anniversary MEN1: from positional cloning to gene function restoration
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - September 12, 2017 Category: Endocrinology Authors: Weber, F., Mulligan, L. M. Tags: Editorials Source Type: research
The microenvironment induces collective migration in SDHB-silenced mouse pheochromocytoma spheroids
In this study, we demonstrated that SDHB silencing per se increases tumor cell migration/invasion and that microenvironment, as represented by CAFs, plays a pivotal role in enhancing collective migration/invasion in Pheo SDHB-silenced tumor cells, suggesting their role in increasing the tumor metastasizing potential. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - August 22, 2017 Category: Endocrinology Authors: D'Antongiovanni, V., Martinelli, S., Richter, S., Canu, L., Guasti, D., Mello, T., Romagnoli, P., Pacak, K., Eisenhofer, G., Mannelli, M., Rapizzi, E. Tags: Research Source Type: research
Differences in miRNA expression profiles between wild-type and mutated NIFTPs
Noninvasive encapsulated follicular variants of papillary thyroid carcinomas have been recently reclassified as noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs). NIFTPs exhibit a behavior that is very close to that of follicular adenomas but different from the infiltrative and invasive follicular variants of papillary thyroid carcinomas (FVPTCs). The importance of miRNAs to carcinogenesis has been reported in recent years. miRNAs seem to be promising diagnostic and prognostic molecular markers for thyroid cancer, and the combination of miRNA expression and mutational status might impro...
Source: Endocrine-Related Cancer - August 22, 2017 Category: Endocrinology Authors: Denaro, M., Ugolini, C., Poma, A. M., Borrelli, N., Materazzi, G., Piaggi, P., Chiarugi, M., Miccoli, P., Vitti, P., Basolo, F. Tags: Research Source Type: research
Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas
This study was undertaken to explore the molecular characteristics of APAs, specifically focusing on APAs with KCNJ5 mutations as opposed to those without KCNJ5 mutations, by comparing their transcriptome and methylome status. Cortisol-producing adenomas (CPAs) were used as reference. We conducted transcriptome and methylome analyses of 29 APAs with KCNJ5 mutations, 8 APAs without KCNJ5 mutations and 5 CPAs. Genome-wide gene expression and CpG methylation profiles were obtained from RNA and DNA samples extracted from these 42 adrenal tumors. Cluster analysis of the transcriptome and methylome revealed molecular heterogenei...
Source: Endocrine-Related Cancer - August 22, 2017 Category: Endocrinology Authors: Murakami, M., Yoshimoto, T., Nakabayashi, K., Nakano, Y., Fukaishi, T., Tsuchiya, K., Minami, I., Bouchi, R., Okamura, K., Fujii, Y., Hashimoto, K., Hata, K.-i., Kihara, K., Ogawa, Y. Tags: Research Source Type: research
OP449 inhibits breast cancer growth without adverse metabolic effects
Hyperinsulinemia is associated with a decrease in breast cancer recurrence-free survival and overall survival. Inhibition of insulin receptor signaling is associated with glycemic dysregulation. SET is a direct modulator of PP2A, which negatively regulates the PI3K/AKT/mTOR pathway. OP449, a SET inhibitor, decreases AKT/mTOR activation. The effects of OP449 treatment on breast cancer growth in the setting of pre-diabetes, and its metabolic implications are currently unknown. We found that the volumes and weights of human MDA-MB-231 breast cancer xenografts were greater in hyperinsulinemic mice compared with controls (P <...
Source: Endocrine-Related Cancer - August 22, 2017 Category: Endocrinology Authors: Shlomai, G., Zelenko, Z., Antoniou, I. M., Stasinopoulos, M., Tobin-Hess, A., Vitek, M. P., LeRoith, D., Gallagher, E. J. Tags: Research Source Type: research
Acromegaly at diagnosis in 3173 patients from the Liege Acromegaly Survey (LAS) Database
In conclusion, this study of >3100 patients is the largest international acromegaly database and shows clinically relevant trends in the characteristics of acromegaly at diagnosis. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - August 22, 2017 Category: Endocrinology Authors: Petrossians, P., Daly, A. F., Natchev, E., Maione, L., Blijdorp, K., Sahnoun-Fathallah, M., Auriemma, R., Diallo, A. M., Hulting, A.-L., Ferone, D., Hana, V., Filipponi, S., Sievers, C., Nogueira, C., Fajardo-Montanana, C., Carvalho, D., Hana, V., Stalla, Tags: Research Source Type: research
Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance
Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which stu...
Source: Endocrine-Related Cancer - August 22, 2017 Category: Endocrinology Authors: Zabkiewicz, C., Resaul, J., Hargest, R., Jiang, W. G., Ye, L. Tags: Review Source Type: research
