Neuroendocrine Tumors in the Stomach, Duodenum, and Pancreas Accompanied by Novel MEN1 Gene Mutation

Yang, Mingzhe; Lee, Woong Ki; Shin, Hong Shik; Park, Sung Hyun; Kim, Byung Sun; Kim, Ji Woong; Cho, Jin Woong; Yun, So Hee

doi:10.4166/kjg.2017.69.3.181

Cited by 4 publications

(3 citation statements)

References 18 publications

(19 reference statements)

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“…Mutations in the MEN1 gene results in abnormal menin protein production, which leads to MEN1 syndrome, demonstrated by development of multiple NEN tumors. While the studies described earlier focused on patients who have no known genetic syndrome, germline mutations in MEN1 can increase susceptibility to multifocal primary NENs, and such mutations have been identified in midgut NENs ( 28 ), though this is rare.…”

Section: Nonclonal Origin Of Multifocal Nensmentioning

confidence: 99%

The Molecular Biology of Midgut Neuroendocrine Neoplasms

Webster,

Thirlwell

2023

Endocrine Reviews

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Midgut neuroendocrine neoplasms (NENs) are one of the most common subtypes of NEN, and their incidence is rising globally. Despite being the most frequently diagnosed malignancy of the small intestine, little is known about their underlying molecular biology. Their unusually low mutational burden compared to other solid tumours, and the unexplained occurrence of multi-focal tumours makes the molecular biology of midgut NENs a particularly fascinating field of research. This review provides an overview of recent advances in the understanding of the interplay of the genetic, epigenetic and transcriptomic landscape in the development of midgut NENs; a topic which is critical to understanding their biology and improving treatment options and outcomes for patients.

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Section: Nonclonal Origin Of Multifocal Nensmentioning

confidence: 99%

The Molecular Biology of Midgut Neuroendocrine Neoplasms

Webster,

Thirlwell

2023

Endocrine Reviews

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“…MEN1 gene mutations have evolved from inherited tumor syndromes to recognizing the role of somatic MEN1 mutations in sporadic neuroendocrine tumors (37)(38)(39). Advances in tumor genetic profiling of pNETs have identified somatic MEN1 mutations in 30-44% of sporadic islet cell tumors (38,40,41).…”

Section: Multiple Endocrine Neoplasia Type 1 Syndrome (Men1)mentioning

confidence: 99%

Familial Hyperparathyroidism

Blau

Simonds

2021

Front. Endocrinol.

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Regulation of the serum calcium level in humans is achieved by the endocrine action of parathyroid glands working in concert with vitamin D and a set of critical target cells and tissues including osteoblasts, osteoclasts, the renal tubules, and the small intestine. The parathyroid glands, small highly vascularized endocrine organs located behind the thyroid gland, secrete parathyroid hormone (PTH) into the systemic circulation as is needed to keep the serum free calcium concentration within a tight physiologic range. Primary hyperparathyroidism (HPT), a disorder of mineral metabolism usually associated with abnormally elevated serum calcium, results from the uncontrolled release of PTH from one or several abnormal parathyroid glands. Although in the vast majority of cases HPT is a sporadic disease, it can also present as a manifestation of a familial syndrome. Many benign and malignant sporadic parathyroid neoplasms are caused by loss-of-function mutations in tumor suppressor genes that were initially identified by the study of genomic DNA from patients who developed HPT as a manifestation of an inherited syndrome. Somatic and inherited mutations in certain proto-oncogenes can also result in the development of parathyroid tumors. The clinical and genetic investigation of familial HPT in kindreds found to lack germline variants in the already known HPT-predisposition genes represents a promising future direction for the discovery of novel genes relevant to parathyroid tumor development.

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“…The evidence is the strongest for sporadic non-functional pancreatic neuroendocrine tumors (NF PNETs) in which MEN1 mutations are found in up to 30-44% of tumors (Jiao et al 2011, Scarpa et al 2017, Raj et al 2018. Gastric, duodenal and small intestinal NETs may also harbor loss of 11q13 (Yang et al 2017).…”

Section: Introductionmentioning

confidence: 99%

c-MET inhibition: novel treatment for sporadic and MEN1-associated GEP NETs

Lee

Tepede

Mandl

et al. 2020

Journal of Molecular Endocrinology

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Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) comprise a heterogenous and diverse group of neoplasms arising from a common neuroendocrine cell origin. The majority of these tumors occur sporadically while ~20% manifest within the context of hereditary syndromes. Germline MEN1 mutations cause a syndrome with an increased susceptibility to multifocal primary GEP NETs. In addition, MEN1 mutations also occur in sporadic GEP NETs. MEN1 alternations are the most frequent sporadic mutation found in pancreatic neuroendocrine tumors (PNETs). We explore the implication of the loss of the MEN1 encoded protein menin as a key pathogenic driver in subsets of GEP NETs with downstream consequences including upregulation of the oncogenic receptor c-MET (hepatocyte growth factor receptor). This review will summarize the data related to the clinical presentation, therapeutic standards, and outcomes of sporadic and MEN1 associated GEP NETs. We present the data on c-MET expression in GEP NETs, clinical trials using c-MET inhibtors, and provide an overview of the molecular mechanisms by which c-MET inhibition in GEP NETs represents a potential precision-medicine targeted approach.

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Neuroendocrine Tumors in the Stomach, Duodenum, and Pancreas Accompanied by Novel MEN1 Gene Mutation

Cited by 4 publications

References 18 publications

The Molecular Biology of Midgut Neuroendocrine Neoplasms

The Molecular Biology of Midgut Neuroendocrine Neoplasms

Familial Hyperparathyroidism

c-MET inhibition: novel treatment for sporadic and MEN1-associated GEP NETs

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