Multiple endocrine neoplasia type 2 (MEN2) and
            <i>RET</i>
            specific modifications of the ACMG/AMP variant classification guidelines and impact on the MEN2
            <i>RET</i>
            database

Margraf, Rebecca L.; Alexander, Rachel Z.; Fulmer, Makenzie; Miller, Christine; Coupal, Elena; Mao, Rong

doi:10.1002/humu.24486

Cited by 6 publications

(3 citation statements)

References 77 publications

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“…Genes belonging to this cluster include the RET gene and the NF1 gene which are associated with Multiple Endocrine Neoplasia type 2 (MEN2) and with neurofibromatosis type 1 respectively [ 13 , 14 , 19 , 20 ].…”

Section: Genetics and Molecular Classification Of Ppgls: How They Aff...mentioning

confidence: 99%

The Management of Phaeochromocytomas and Paragangliomas in the Era of Precision Medicine: Where Are We Now? Evidence-Based Systemic Treatment Options and Future Cluster Oriented Perspectives

Bracigliano,

Marretta,

Guerrera

et al. 2024

Pharmaceuticals

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Pheochromocytomas (PCCs) and Paragangliomas (PGLs), commonly known as PPGLs to include both entities, are rare neuroendocrine tumors that may arise in the context of hereditary syndromes or be sporadic. However, even among sporadic PPGLs, identifiable somatic alterations in at least one of the known susceptibility genes can be detected. Therefore, about 3/4 of all PPGL patients can be assigned to one of the three molecular clusters that have been identified in the last years with difference in the underlying pathogenetic mechanisms, biochemical phenotype, metastatic potential, and prognosis. While surgery represents the mainstay of treatment for localized PPGLs, several therapeutic options are available in advanced and/or metastatic setting. However, only few of them hinge upon prospective data and a cluster-oriented approach has not yet been established. In order to render management even more personalized and improve the prognosis of this molecularly complex disease, it is undoubtable that genetic testing for germline mutations as well as genome profiling for somatic mutations, where available, must be improved and become standard practice. This review summarizes the current evidence regarding diagnosis and treatment of PPGLs, supporting the need of a more cluster-specific approach in clinical practice.

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Section: Genetics and Molecular Classification Of Ppgls: How They Aff...mentioning

confidence: 99%

The Management of Phaeochromocytomas and Paragangliomas in the Era of Precision Medicine: Where Are We Now? Evidence-Based Systemic Treatment Options and Future Cluster Oriented Perspectives

Bracigliano,

Marretta,

Guerrera

et al. 2024

Pharmaceuticals

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“…The main pathogenic hotspots in MEN2A are located in the RET cysteine-rich domain- exon 10 (codons 609, 611, 618, or 620) and exon 11 (codons 630 and 634). Codon 634 pathogenic variants are associated with a higher risk of developing pheochromocytoma and pruritic cutaneous lichen amyloidosis [ 101 , 102 , 103 , 104 ]. Cases with MEN2A and Hirschprung disease usually have pathogenic variants in exon 10.…”

Section: Cancer Predisposition Syndromes With Thyroid Cancermentioning

confidence: 99%

Cancer Predisposition Syndromes and Thyroid Cancer: Keys for a Short Two-Way Street

Balinisteanu,

Panzaru,

Caba

et al. 2023

Biomedicines

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Cancer predisposition syndromes are entities determined especially by germinal pathogenic variants, with most of them autosomal dominantly inherited. The risk of a form of cancer is variable throughout life and affects various organs, including the thyroid. Knowing the heterogeneous clinical picture and the existing genotype–phenotype correlations in some forms of thyroid cancer associated with these syndromes is important for adequate and early management of patients and families. This review synthesizes the current knowledge on genes and proteins involved in cancer predisposition syndromes with thyroid cancer and the phenomena of heterogeneity (locus, allelic, mutational, and clinical).

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“…For rarer RET sequence variants, consulting the ARUP MEN2 database is worthwhile (https://arup.utah.edu/database/ MEN2/MEN2_display.phpis). This online gene repository provides a valuable source of genomic information about the pathogenicity of RET sequence variants from worldwide sources [21,22].…”

Section: Key Pointsmentioning

confidence: 99%

Multiple endocrine neoplasia type 2: towards a risk-based approach integrating molecular and biomarker results

Machens,

Dralle

2023

Current Opinion in Oncology

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Purpose of review Significant advances have transformed our understanding of the molecular biology and natural history of multiple endocrine neoplasia type 2 (MEN2). This progress enacted a paradigm shift with regard to routine neck dissection for medullary thyroid cancer and total adrenalectomy for pheochromoytoma. The purpose of this review is to summarize key molecular and clinical data underpinning the current risk-based approach to MEN2 that integrates molecular and biomarker results. Recent findings Early identification and biochemical monitoring of rearranged during transfection (RET) carriers yield important lead time. Within these ‘windows of opportunity’, total thyroidectomy alone, avoiding incremental morbidity from node dissection; ‘tissue-sparing’ subtotal adrenalectomy, balancing risks of steroid dependency with pheochromocytoma recurrence in adrenal remnants; and parathyroidectomy of enlarged glands only, weighing risks of postoperative hypoparathyroidism against hyperactive parathyroid glands left behind, are adequate therapies. Summary All that is needed to determine a RET carriers’ risk of medullary thyroid cancer, pheochromocytoma and/or primary hyperparathyroidism in the molecular era is patient age, underlying RET mutation, and biomarker levels. As broader testing begins to penetrate healthcare, the needle on population genomic screening and education needs to be moved forward to complete the transition from symptom-based to preventive healthcare.

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Multiple endocrine neoplasia type 2 (MEN2) and RET specific modifications of the ACMG/AMP variant classification guidelines and impact on the MEN2 RET database

Cited by 6 publications

References 77 publications

The Management of Phaeochromocytomas and Paragangliomas in the Era of Precision Medicine: Where Are We Now? Evidence-Based Systemic Treatment Options and Future Cluster Oriented Perspectives

The Management of Phaeochromocytomas and Paragangliomas in the Era of Precision Medicine: Where Are We Now? Evidence-Based Systemic Treatment Options and Future Cluster Oriented Perspectives

Cancer Predisposition Syndromes and Thyroid Cancer: Keys for a Short Two-Way Street

Multiple endocrine neoplasia type 2: towards a risk-based approach integrating molecular and biomarker results

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