Prevalence of the major thyroid cancer-associated syndromes in the United States.

Importance: A subset of thyroid cancers develops in a setting of a known hereditary cancerassociated syndrome. Understanding the population prevalence of thyroid cancer-associated syndromes is important to guide germline genetic testing and clinical management.

Objective: To estimate the prevalence of the major thyroid cancer-associated syndromes in the United States using the All of Us Research Program (AoU) data.

Mechanisms of resistance to RET-directed therapies.

The association between RET and multiple endocrine neoplasia type 2 was established in 1993 and remains one of the very few oncogenes for which distinct phenotypes (medullary thyroid cancer or phaeochromocytoma) are associated with the same hot-spot variants occurring either in germline or somatic DNA. Somatic RET fusion events have also been described in several cancers, including papillary thyroid cancer, non-small cell lung cancer, breast cancer, salivary gland cancer and pancreatic cancer. Highly selective RET inhibitors have improved outcomes in RET-altered cancers and have been well tolerated.

Targeting Menin in Acute Myeloid Leukemia: Therapeutic Advances and Future Directions.

Germline mutations in the gene encoding menin protein cause multiple endocrine neoplasia type 1 (MEN1) syndrome. Recent evidence suggests that inhibiting the interaction of menin with its crucial oncogenic protein partners represents a promising therapeutic strategy to AML. Menin plays a critical role in lysine methyltransferase 2A ()-gene-rearranged and -m acute leukemias, both associated with adverse outcomes with current standard therapies, especially in the relapsed/refractory setting.

Endocrine Perspective of Cutaneous Lichen Amyloidosis: -C634 Pathogenic Variant in Multiple Endocrine Neoplasia Type 2.

Background: Medullary thyroid carcinoma (MTC), the third most frequent histological type of thyroid malignancy, may be found isolated or as part of multiple endocrine neoplasia type 2 (MEN2). One particular subtype of this autosomal dominant-transmitted syndrome includes an association with cutaneous lichen amyloidosis, although, generally, a tide genotype-phenotype correlation is described in patients who carry proto-oncogene pathogenic variants.

Methods: Our objective was to provide an endocrine perspective of a case series diagnosed with -positive familial MTC associated with cutaneous primary lichen amyloidosis amid the confirmation of MEN2.

A Case of Cushing's Disease and a RET Pathogenic Variant: Exploring Possible Rare Associations.

Cushing disease (CD), a rare endocrine disorder characterized by a pituitary adenoma that secretes excess adrenocorticotropic hormone (ACTH), leads to overproduction of cortisol by the adrenal glands and, depending on severity and duration, manifests with a broad spectrum of clinical signs and symptoms, ranging from classical features to more common conditions seen in the general population. Discovery of molecular and pathogenic mechanisms related to the development of CD tumors has increased in recent years, almost two-thirds of the somatic variants cases have been linked to the USP8 gene, while very rare germline variants in MEN1 and AIP genes have been associated with pituitary adenomas. Variants affecting the RET proto-oncogene, which encodes a receptor tyrosine kinase involved in cell growth and differentiation, are implicated in the development of medullary thyroid carcinoma (MTC) and its hereditary form, multiple endocrine neoplasia type 2 (MEN2).

Molecular diagnostic approaches in detecting rearranged during transfection oncogene mutations in multiple endocrine neoplasia type 2.

Different types of neuroendocrine cancer, including medullary thyroid cancer (MTC) and thyroid C-cell hyperplasia, are part of multiple endocrine neoplasia type 2 (MEN2). A proto-oncogene mutation of the rearranged during transfection () gene changes the way that receptor tyrosine kinases work. Multiple endocrine neoplasia, a pathological condition, involves these kinases.

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MANAGING MEDULLARY THYROID CARCINOMA IN 2024: Medullary thyroid carcinoma is a rare neuroendocrine thyroid cancer with a heterogeneous prognosis which has the particularity of being associated with a RET gene mutation, germline in 20-25% of cases in the context of multiple endocrine neoplasia type 2 (NEM2), and somatic in 70% of sporadic cases. It is often diagnosed on a thyroid nodule or in the context of genetic screening. Calcitonin is a biological marker, used for diagnosis, monitoring of therapeutic response and prognostic evaluation.

Living with a RET gene mutation: patient perspectives.

Multiple endocrine neoplasia type 2 (MEN2) is the collective term for two distinct types of autosomal dominantly inherited neuroendocrine neoplasm syndromes: MEN2A and MEN2B (or MEN3). MEN2 is characterised by medullary thyroid cancer (MTC) (99%) and phaeochromocytoma (50%) and also other conditions according to specific genotype. MEN2A also includes a 25% risk of developing parathyroid hyperplasia and is now recognised as four separate syndromes: classic MEN2A, MEN2A with cutaneous lichen amyloidosis, MEN2A with Hirschsprung's disease and familial MTC.

Cellular mechanisms of RET receptor dysfunction in multiple endocrine neoplasia 2.

Abstract: Rearranged during transfection (RET) is a developmentally important receptor tyrosine kinase that has been identified as an oncogenic driver in a number of cancers. Activating RET point mutations gives rise to the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2), characterized by medullary thyroid carcinoma. There are two MEN2 subtypes, MEN2A and MEN2B, that differ in tumour aggressiveness and the associated constellation of other disease features, which are caused by distinct patterns of RET amino acid substitution mutations.

Sporadic and Familial Medullary Thyroid Carcinoma: A Retrospective Single Center Study on Presentation and Outcome.

Background: Medullary Thyroid Carcinoma (MTC) is a neuroendocrine tumor that arises from the thyroid C-cells. Most cases are sporadic (sMTC) while, approximately 25%, are hereditary (hMTC) due to germline mutations of REarranged during Transfection (RET) gene mutations and manifest in the framework of multiple endocrine neoplasia (MEN) 2A or 2B, or as pure familial MTC syndrome (FMTC).

Objective: The aim of this study is to evaluate the clinical, histopathological, biochemical and outcome differences between sMTC and hMTC.

Genotype/phenotype correlations in multiple endocrine neoplasia type 2.

Abstract: Multiple endocrine neoplasia type 2 (MEN 2) is a rare hereditary endocrine tumor syndrome caused by mutations in the rearranged during transfection (RET) gene. MEN 2 is divided into two main entities, MEN 2A and MEN 2B, both of which present with medullary thyroid cancer (MTC) in approximately 100% of cases and pheochromocytoma in 50% of cases. Specific RET mutations are associated with a risk of early onset of MTC, from 1 year of age (highest risk) to 5 years of age (high risk).

Approach to the patient with thyroid nodules: considering GLP-1 receptor agonists.

Glucagon-like peptide 1 receptor agonists (GLP1RA) have rapidly changed the landscape of diabetes and obesity treatment. Enthusiasm for their use is tempered with concerns regarding their risk for inducing C-cell tumors based on preclinical studies in rodents. A black-box warning from the United States Food and Drug Administration (USFDA) recommends against using GLP1RA in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2A or 2B (MEN2), providing clear guidance regarding this cohort of patients.