1,607 results match your criteria Medullary Thyroid Cancer and RET


Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study.

Endocr Connect 2019 Feb 1. Epub 2019 Feb 1.

A Maia, INTERNAL MEDICINE, UNIVERSIDADE FEDERAL DO RIO GRANDE DO SUL, Porto Alegre, 90035-003, Brazil.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumours. Several reports have demonstrated that the RET mutation profile may vary according to geographical area. In this study we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries. Read More

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http://dx.doi.org/10.1530/EC-18-0506DOI Listing
February 2019

[Familial medullary thyroid carcinoma: case report and literature review.]

Rev Fac Cien Med Univ Nac Cordoba 2018 12 12;75(4):303-309. Epub 2018 Dec 12.

Instituto Nacional de Enfermedades Neoplásicas Universidad Nacional Mayor de San Marcos.

Medullary thyroid carcinoma (MTC) is a malignant tumour of the calcitonin-secreting parafollicular C cells of the thyroid gland. Up to 25% of MTC are associated to pathogenic germinal variants on the proto-oncogene RET (locus 10q11.2), which cause Familial Medullary Thyroid Carcinoma (FMTC) or Multiple Endocrine Neoplasia type 2 (MEN2); genetic conditions inherited with autosomal dominant pattern. Read More

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http://dx.doi.org/10.31053/1853.0605.v75.n4.20947DOI Listing
December 2018

Management of Medullary Thyroid Cancer.

Endocrinol Metab Clin North Am 2019 03 26;48(1):285-301. Epub 2018 Dec 26.

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Paradisa 2, Pisa 56124, Italy. Electronic address:

Medullary thyroid cancer (MTC) is rare but aggressive. It can be cured only if intrathyroid at diagnosis. MTC can be sporadic (75%) or familial (25%) and the 2 forms are distinguished by RET mutations analysis. Read More

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http://dx.doi.org/10.1016/j.ecl.2018.11.006DOI Listing
March 2019
2 Reads

Preclinical characterization of tyrosine kinase inhibitor-based targeted therapies for neuroendocrine thyroid cancer.

Oncotarget 2018 Dec 28;9(102):37662-37675. Epub 2018 Dec 28.

Department of Surgery, The University of Alabama, Birmingham, AL, USA.

Medullary thyroid carcinoma (MTC) is a slow growing neuroendocrine (NE) tumor for which few treatment options are available. Its incidence is rising and mortality rates have remained unchanged for decades. Increasing the repertoire of available treatments is thus crucial to manage MTC progression. Read More

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http://www.oncotarget.com/fulltext/26480
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http://dx.doi.org/10.18632/oncotarget.26480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340867PMC
December 2018
6 Reads

Completeness of testing in patients with medullary thyroid carcinoma in Denmark 1997-2013: a nationwide study.

Clin Epidemiol 2019 10;11:93-99. Epub 2019 Jan 10.

Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark,

Background: The completeness of arranged during ransfection () testing in patients with medullary thyroid carcinoma (MTC) was recently reported as 60%. However, the completeness on a population level is unknown. Similarly, it is unknown if the first Danish guidelines from 2002, recommending testing in all MTC patients, improved completeness in Denmark. Read More

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http://dx.doi.org/10.2147/CLEP.S183268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330966PMC
January 2019
1 Read

Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study.

Lancet Diabetes Endocrinol 2019 Jan 16. Epub 2019 Jan 16.

Endocrine Oncology, Institut Gustave Roussy Ecole Doctorale de Cancerologie, Villejuif, France.

Background: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22138587183033
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http://dx.doi.org/10.1016/S2213-8587(18)30336-XDOI Listing
January 2019
6 Reads

Modeling malignancies using induced pluripotent stem cells: from chronic myeloid leukemia to hereditary cancers.

Exp Hematol 2019 Jan 16. Epub 2019 Jan 16.

INSERM UMR-S 935 and ESTeam Paris Sud, Université Paris Sud, Villejuif, France; INGESTEM National iPSC Infrastructure, Villejuif, France.

Over the last decade, the possibility of reprogramming malignant cells to a pluripotent state has been achieved in several hematological malignancies, including myeloproliferative neoplasms, myelodysplastic syndromes, and chronic myeloid leukemia (CML). It has been shown that it is readily possible to generate induced pluripotent stem cells (iPSCs) from several types of primary CML cells and to generate progenitors and differentiated cells with variable efficiency. Although these experiments have brought some new insights in the understanding of CML pathophysiology, the ultimate goal of generating induced leukemic stem cells (LSCs) with long-term multilineage potential has not yet been demonstrated. Read More

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http://dx.doi.org/10.1016/j.exphem.2019.01.003DOI Listing
January 2019
2 Reads

Metabolomics signatures of a subset of RET variants according to their oncogenic risk level.

Endocr Relat Cancer 2019 Jan 1. Epub 2019 Jan 1.

D Mirebeau-Prunier, Biochemistry, Centre Hospitalier Universitaire d\'Angers, ANGERS, France.

Thirty percent of medullary thyroid carcinomas (MTC) are related to dominant germline pathogenic variants in the RET proto-oncogene. According to their aggressiveness, these pathogenic variants are classified in three risk levels: 'moderate', 'high' and 'highest'. The present study compares the metabolomics profiles of five pathogenic variants, whether already classified or not. Read More

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http://dx.doi.org/10.1530/ERC-18-0314DOI Listing
January 2019
1 Read

A pioneering RET genetic screening study in the State of Ceará, Brazil, evaluating patients with medullary thyroid cancer and at-risk relatives: experience with 247 individuals.

Arch Endocrinol Metab 2018 ;62(6):623-635

Centro de Doenças da Tiroide e Laboratório de Endocrinologia Molecular e Translacional, Divisão de Endocrinologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brasil.

Objective: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening.

Subjects And Methods: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Read More

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http://dx.doi.org/10.20945/2359-3997000000088DOI Listing
February 2019
1 Read

An Unusual Case of Medullary Thyroid Carcinoma and a revision of current literature.

Endocr Metab Immune Disord Drug Targets 2018 Dec 20. Epub 2018 Dec 20.

University-Hospital "Santa Maria della Misericordia", Udine, Endocrinology and Metabolism Unit Udine. Italy.

Background: Medullary thyroid cancer (MTC) accounts for 5% of all thyroid cancers and occurs either sporadically or in a hereditary pattern. Routine calcitonin (CT) measurement is suggested for MTC screening in patients with nodular thyroid disease. Patient Findings A 45 years-old woman incidentally discovered, with neck ultrasound, the presence of thyroid micronodules. Read More

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http://dx.doi.org/10.2174/1871530319666181220165350DOI Listing
December 2018
3 Reads

Combinations of Tyrosine Kinase Inhibitor and ERAD Inhibitor Promote Oxidative Stress-Induced Apoptosis through ATF4 and KLF9 in Medullary Thyroid Cancer.

Mol Cancer Res 2018 Dec 14. Epub 2018 Dec 14.

Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Medullary thyroid carcinoma (MTC) originates from the C cells of the thyroid gland, which secrete calcitonin. Lymph node and distant metastases are frequently present at diagnosis. Activating mutations of , a driver oncogene in MTC that encodes a tyrosine kinase receptor, prevents apoptosis through inhibition of ATF4, a key transcriptional regulator of endoplasmic reticulum (ER) stress. Read More

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http://mcr.aacrjournals.org/lookup/doi/10.1158/1541-7786.MCR
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http://dx.doi.org/10.1158/1541-7786.MCR-18-0354DOI Listing
December 2018
9 Reads

Medullary thyroid carcinoma with breast metastasis: Two case reports.

Medicine (Baltimore) 2018 Nov;97(47):e13193

Department of Surgical Oncology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.

Rationale: Medullary thyroid carcinoma (MTC) is an aggressive subtype of thyroid cancer with frequent hematogenous metastasis. While its metastasis is usually observed in the lung, liver, or bone, it rarely migrates to the breast.

Patient Concerns: Here we report 2 cases with a complaint of breast lump after initial treatment of MTC. Read More

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http://dx.doi.org/10.1097/MD.0000000000013193DOI Listing
November 2018
7 Reads

Genetic characterization of medullary thyroid cancer in childhood survivors of the Chernobyl accident.

Surgery 2019 Jan 2;165(1):58-63. Epub 2018 Nov 2.

University of Texas MD Anderson Cancer Center, Department of Surgical Oncology, Houston, Texas. Electronic address:

Background: Radiation-associated fusion oncogenes play a direct role in papillary thyroid cancer development and pathogenic fusions have recently been reported in medullary thyroid cancer. To date, no studies have evaluated oncogenic events in medullary thyroid cancer in a radiation-exposed population.

Methods: Somatic and germline alterations, including RET fusions, were evaluated in paired medullary thyroid cancer tumor and normal samples from the Chernobyl Tissue Bank, a heavily screened population affected by the Chernobyl disaster. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00396060183057
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http://dx.doi.org/10.1016/j.surg.2018.08.029DOI Listing
January 2019
9 Reads

A synonymous RET substitution enhances the oncogenic effect of an in-cis missense mutation by increasing constitutive splicing efficiency.

PLoS Genet 2018 10 15;14(10):e1007678. Epub 2018 Oct 15.

Department of Internal Medicine and Medical Specialties, "Sapienza" University of Rome, Rome, Italy.

Synonymous mutations continue to be filtered out from most large-scale cancer genome studies, but several lines of evidence suggest they can play driver roles in neoplastic disease. We investigated a case of an aggressive, apparently sporadic medullary thyroid carcinoma (MTC) harboring a somatic RET p.Cys634Arg mutation (a known MTC driver). Read More

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http://dx.doi.org/10.1371/journal.pgen.1007678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201961PMC
October 2018
4 Reads

Phase I/II Trial of Vandetanib and Bortezomib in Adults with Locally Advanced or Metastatic Medullary Thyroid Cancer.

Oncologist 2019 Jan 8;24(1):16-e14. Epub 2018 Oct 8.

Medstar Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA.

Lessons Learned: Vandetanib at a dose of 300 mg orally every day plus bortezomib 1.3 mg/m intravenously on days 1, 4, 8, and 11 could be administered safely.Assessing outcomes in 17 patients with medullary thyroid cancer, investigators considered the combination to be more difficult to administer than single-agent vandetanib and that achieving better outcomes was unlikely. Read More

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http://dx.doi.org/10.1634/theoncologist.2018-0452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324636PMC
January 2019
6 Reads

Volumetric and texture analysis of pretherapeutic F-FDG PET can predict overall survival in medullary thyroid cancer patients treated with Vandetanib.

Endocrine 2018 Sep 11. Epub 2018 Sep 11.

Department of Nuclear Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.

Purpose: The metabolically most active lesion in 2-deoxy-2-(F)fluoro-D-glucose (F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic F-FDG PET. Read More

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http://dx.doi.org/10.1007/s12020-018-1749-3DOI Listing
September 2018
3 Reads

The Reality of Multiple Endocrine Neoplasia Type 2B Diagnosis: Awareness of Unique Physical Appearance Is Important.

J Nippon Med Sch 2018 ;85(3):178-182

Department of Endocrine Surgery, Nippon Medical School.

Background: Multiple endocrine neoplasia type 2B (MEN2B) is an extremely rare syndrome mainly caused by RET918 germline mutations. MEN2B typically causes medullary thyroid carcinoma (MTC), pheochromocytoma, and unique physical characteristics including mucosal neuroma, distinctive facial appearance, and Marfanoid habitus. Most patients have abdominal symptoms such as bloating, intermittent constipation, and diarrhea. Read More

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http://dx.doi.org/10.1272/jnms.JNMS.2018_85-26DOI Listing
October 2018
3 Reads

Transcriptional targeting of oncogene addiction in medullary thyroid cancer.

JCI Insight 2018 Aug 23;3(16). Epub 2018 Aug 23.

Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University Wexner Medical Center and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA.

Metastatic medullary thyroid cancer (MTC) is incurable and FDA-approved kinase inhibitors that include oncogenic RET as a target do not result in complete responses. Association studies of human MTCs and murine models suggest that the CDK/RB pathway may be an alternative target. The objective of this study was to determine if CDKs represent therapeutic targets for MTC and to define mechanisms of activity. Read More

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https://insight.jci.org/articles/view/122225
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http://dx.doi.org/10.1172/jci.insight.122225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141185PMC
August 2018
13 Reads

Pheochromocytoma in Children and Adolescents With Multiple Endocrine Neoplasia Type 2B.

J Clin Endocrinol Metab 2019 Jan;104(1):7-12

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland.

Context: Multiple endocrine neoplasia type 2B (MEN2B) is characterized by early-onset medullary thyroid cancer in virtually all cases and a 50% lifetime risk of pheochromocytoma (PHEO) development. The literature on PHEO in patients with MEN2B is limited with most data being reported from adult studies that primarily address MEN2A.

Objective: The aim of the current study is to describe PHEO development in a cohort of pediatric patients with MEN2B. Read More

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https://academic.oup.com/jcem/advance-article/doi/10.1210/jc
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http://dx.doi.org/10.1210/jc.2018-00705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240163PMC
January 2019
18 Reads

Update on Multiple Endocrine Neoplasia Type 2: Focus on Medullary Thyroid Carcinoma.

J Endocr Soc 2018 Aug 13;2(8):933-943. Epub 2018 Jul 13.

Endocrine Practice Heidelberg, Molecular Genetic Laboratory, Heidelberg, Germany.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant hereditary cancer syndrome caused by missense gain-of-function mutations in the proto-oncogene on chromosome 10. Specific mutations can predispose toward a particular phenotype and clinical course, with strong genotype-phenotype correlations. MEN2 is highly penetrant in medullary thyroid carcinoma (MTC), and it can be associated with bilateral pheochromocytoma and primary hyperparathyroidism. Read More

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http://dx.doi.org/10.1210/js.2018-00178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065486PMC
August 2018
16 Reads

Cabozantinib: Multi-kinase Inhibitor of MET, AXL, RET, and VEGFR2.

Recent Results Cancer Res 2018;211:67-75

Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Medical Center, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany.

Cabozantinib is a receptor tyrosine kinase inhibitor (TKI) with activity against a broad range of targets, including MET, RET, AXL, VEGFR2, FLT3, and c-KIT. Activity of cabozantinib towards a broad range of tumor models could be detected in several preclinical studies. Of note, cabozantinib decreases metastasis potential and tumor invasiveness when compared with placebo or agents that target VEGFR and have no activity against MET. Read More

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http://dx.doi.org/10.1007/978-3-319-91442-8_5DOI Listing
November 2018
1 Read

Regorafenib.

Recent Results Cancer Res 2018;211:45-56

Department of Internal Medicine I, University of Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany.

Regorafenib (BAY 73-4506, Stivarga) is an oral diphenylurea multi-kinase inhibitor that targets angiogenic (VEGFR1-3, TIE2), stromal (PDGFR-β, FGFR), and oncogenic receptor tyrosine kinases (KIT, RET, and RAF). Regorafenib is the first small-molecule multi-kinase inhibitor to achieve survival benefits in metastatic colorectal cancer that has progressed after all standard therapies. Consequently, Regorafenib was FDA approved for this indication in 2012. Read More

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http://dx.doi.org/10.1007/978-3-319-91442-8_3DOI Listing
November 2018
2 Reads

The RET C611Y mutation causes MEN 2A and associated cutaneous lichen amyloidosis.

Endocr Connect 2018 Jul 26. Epub 2018 Jul 26.

J Zhao, Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou , China.

Background: Cutaneous lichen amyloidosis (CLA) has been reported in some multiple endocrine neoplasia type 2A (MEN 2A) families affected by specific germline RET mutations C634F/G/R/W/Y or V804M, as a characteristic of the clinical manifestation in 'MEN 2A with CLA', one of four variants of MEN 2A, which was strictly located in the scapular region of the upper back.

Patient Findings: This study reports a large south-eastern Chinese pedigree with 17 individuals carrying the MEN 2A-harbouring germline C611Y (c.1832G>A) RET mutation by Sanger sequencing. Read More

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http://dx.doi.org/10.1530/EC-18-0220DOI Listing
July 2018
3 Reads

Response to Letter to the Editor: "p.Val804Met, the Most Frequent Pathogenic Mutation in RET, Confers a Very Low Lifetime Risk of Medullary Thyroid Cancer".

J Clin Endocrinol Metab 2018 Sep;103(9):3518-3519

Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom.

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http://dx.doi.org/10.1210/jc.2018-01094DOI Listing
September 2018
5 Reads

Genomic Profiling Reveals Medullary Thyroid Cancer Misdiagnosed as Lung Cancer.

Case Rep Oncol 2018 May-Aug;11(2):399-403. Epub 2018 Jun 22.

Division of Hematology and Oncology, Mayo Clinic Hospital, Phoenix, Arizona, USA.

Mutations or other alterations in the gene have been implicated in a variety of malignancies - most commonly thyroid, but also chronic myelomonocytic leukemia, acute myeloid leukemia, and lung, breast, pancreatic, and colon cancers. Here we present a case of a gentlemen initially diagnosed with and treated for non-small cell lung adenocarcinoma. Genomic profiling of his tumor specimen revealed a point mutation with a known association with medullary thyroid cancer (MTC). Read More

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http://dx.doi.org/10.1159/000490238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047557PMC
June 2018
13 Reads

Multiple Endocrine Neoplasia Syndromes from Genetic and Epigenetic Perspectives.

Biomark Insights 2018 2;13:1177271918785129. Epub 2018 Jul 2.

Chronic Diseases Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Multiple endocrine neoplasia (MEN) syndromes are infrequent inherited disorders in which more than one endocrine glands develop noncancerous (benign) or cancerous (malignant) tumors or grow excessively without forming tumors. There are 3 famous and well-known forms of MEN syndromes (MEN 1, MEN 2A, and MEN 2B) and a newly documented one (MEN4). These syndromes are infrequent and occurred in all ages and both men and women. Read More

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http://dx.doi.org/10.1177/1177271918785129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043927PMC
July 2018
13 Reads

65 YEARS OF THE DOUBLE HELIX: Endocrine tumour syndromes in children and adolescents.

Endocr Relat Cancer 2018 08;25(8):T221-T244

Department of Human GeneticsResearch Institute of the McGill University Health Centre, and Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Canada

As medicine is poised to be transformed by incorporating genetic data in its daily practice, it is essential that clinicians familiarise themselves with the information that is now available from more than 50 years of genetic discoveries that continue unabated and increase by the day. Endocrinology has always stood at the forefront of what is called today 'precision medicine': genetic disorders of the pituitary and the adrenal glands were among the first to be molecularly elucidated in the 1980s. The discovery of two endocrine-related genes, and , both identified in the late 1980s, contributed greatly in the understanding of cancer and its progression. Read More

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http://dx.doi.org/10.1530/ERC-18-0160DOI Listing
August 2018
14 Reads

Educational Case: Endocrine Neoplasm: Medullary Thyroid Carcinoma.

Acad Pathol 2018 Jan-Dec;5:2374289518775722. Epub 2018 Jun 17.

Montefiore Hospital and Medical Center, Bronx, NY, USA.

Medullary thyroid cancer is a rare neuroendocrine tumor that arises the neural crest-derived parafollicular C cells and accounts for approximately 5% to 10% of thyroid cancers worldwide. These tumor can occur sporadically or as part of hereditary tumor syndromes, such as multiple endocrine neoplasia 2 and familial medullary thyroid cancer. The most common clinical presentation is a solitary thyroid nodule. Read More

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http://dx.doi.org/10.1177/2374289518775722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024338PMC
June 2018
4 Reads

Utilization of Genetic Testing for RET Mutations in Patients with Medullary Thyroid Carcinoma: a Single-Center Experience.

J Genet Couns 2018 Dec 27;27(6):1411-1416. Epub 2018 Jun 27.

Genetics Department, Southern California Kaiser Permanente, 6041 Cadillac Ave, Los Angeles, CA, 90034, USA.

Medullary thyroid carcinoma (MTC) is often due to the hereditary condition multiple endocrine neoplasia type 2 (MEN2) and it is standard of care to offer genetic testing to all diagnosed patients. This study used the Kaiser Permanente integrated medical record system to identify patients at risk for MEN2, assess adherence to clinical practice guidelines, and offer genetic counseling and testing. A query of the electronic medical records system identified patients with MTC. Read More

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http://dx.doi.org/10.1007/s10897-018-0273-1DOI Listing
December 2018
13 Reads

Letter to the Editor: "p.Val804Met, the Most Frequent Pathogenic Mutation in RET, Confers a Very Low Lifetime Risk of Medullary Thyroid Cancer".

J Clin Endocrinol Metab 2018 Sep;103(9):3516-3517

Department of General, Visceral and Transplantation Surgery, Section of Endocrine Surgery, University of Duisburg-Essen, Essen, Germany.

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http://dx.doi.org/10.1210/jc.2018-00906DOI Listing
September 2018
3 Reads

Selective RET kinase inhibition for patients with RET-altered cancers.

Ann Oncol 2018 Aug;29(8):1869-1876

Memorial Sloan Kettering Cancer Center, New York, USA.

Background: Alterations involving the RET kinase are implicated in the pathogenesis of lung, thyroid and other cancers. However, the clinical activity of multikinase inhibitors (MKIs) with anti-RET activity in RET-altered patients appears limited, calling into question the therapeutic potential of targeting RET. LOXO-292 is a selective RET inhibitor designed to inhibit diverse RET fusions, activating mutations and acquired resistance mutations. Read More

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http://dx.doi.org/10.1093/annonc/mdy137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096733PMC
August 2018
2 Reads

Diagnostic value and lymph node metastasis prediction of a custom‑made panel (thyroline) in thyroid cancer.

Oncol Rep 2018 Aug 14;40(2):659-668. Epub 2018 Jun 14.

Department of Endocrinology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.

Differentiation of benign and malignant thyroid nodules is crucial for clinical management. Here, we explored the efficacy of next‑generation sequencing (NGS) in predicting the classification of benign and malignant thyroid nodules and lymph node metastasis status, and simultaneously compared the results with ultrasound (US). Thyroline was designed to detect 15 target gene mutations and 2 fusions in 98 formalin‑fixed, paraffin‑embedded (FFPE) tissues, including those from 82 thyroid cancer (TC) patients and 16 patients with benign nodules. Read More

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http://dx.doi.org/10.3892/or.2018.6493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072293PMC
August 2018
18 Reads

Genotypic characteristics and their association with phenotypic characteristics of hereditary medullary thyroid carcinoma in Korea.

Surgery 2018 08 17;164(2):312-318. Epub 2018 May 17.

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Background: Hereditary medullary thyroid carcinoma can present as a part of multiple endocrine neoplasia syndrome by rearranged during transfection gene mutation. We evaluated the prevalence of rearranged during transfection gene mutation in patients who have medullary thyroid carcinoma and the correlations of genotype with medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism according to the revised American Thyroid Association risk level.

Methods: A total of 331 patients were diagnosed with medullary thyroid carcinoma, 172 of whom were tested for the rearranged during transfection germline mutation by sequencing of exon 8, 10, 11, and 13-16. Read More

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http://dx.doi.org/10.1016/j.surg.2018.03.018DOI Listing
August 2018
16 Reads

Incidence and prevalence of sporadic and hereditary MTC in Denmark 1960-2014: a nationwide study.

Endocr Connect 2018 Jun 14;7(6):829-839. Epub 2018 May 14.

Department of ORL Head & Neck SurgeryOdense University Hospital, Odense, Denmark.

Recent studies have shown a significant increase in the temporal trend of medullary thyroid carcinoma (MTC) incidence. However, it remains unknown to which extent sporadic medullary thyroid carcinoma (SMTC) and hereditary MTC (HMTC) affect the MTC incidence over time. We conducted a nationwide retrospective study using previously described and MTC cohorts combined with review of medical records, pedigree comparison and relevant nationwide registries. Read More

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http://dx.doi.org/10.1530/EC-18-0157DOI Listing
June 2018
8 Reads

Rapid methods to create a positive control and identify the rearrangement in FNA thyroid samples by molecular biology.

Oncotarget 2018 Apr 10;9(27):19255-19262. Epub 2018 Apr 10.

Functional Genomics Unit, Istituto Nazionale Tumori -IRCCS -Fondazione G. Pascale, Napoli, Italia.

Thyroid cancer is the most common malignancy of the endocrine system and includes well-differentiated forms, namely papillary and follicular carcinomas, and the poorly differentiated and undifferentiated forms that result from the transformation of thyroid follicular cells (anaplastic carcinomas). Notably, 5-10% of all thyroid cancers are medullary thyroid cancers that arise from parafollicular cells also known as C cells. The most common genetic mutations in papillary and follicular thyroid cancers are point mutations of the or genes, while the most common chromosomal alterations are and rearrangements. Read More

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http://www.oncotarget.com/fulltext/24995
Publisher Site
http://dx.doi.org/10.18632/oncotarget.24995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922393PMC
April 2018
5 Reads

EF24 (a Curcumin Analog) and ZSTK474 Emphasize the Effect of Cabozantinib in Medullary Thyroid Cancer.

Endocrinology 2018 06;159(6):2348-2360

Endocrinology Unit, Department of Medicine, Padua University Hospital, Padova, Italy.

XL184 is a small-molecule kinase inhibitor recently included in first-line systemic therapy for patients with advanced, progressive medullary thyroid cancer (MTC). EF24 is a curcumin analog with a high bioavailability, and ZSTK474 is an inhibitor of the phosphatidylinositol 3-kinase signaling pathway. We investigated the effect of these compounds, alone and in combination, in two rearranged during transfection (RET)-mutated TT and MZ-CRC-1 MTC cell lines and in six mostly RET wild-type human MTC primary cultures. Read More

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http://dx.doi.org/10.1210/en.2018-00124DOI Listing
June 2018
6 Reads

Intraocular metastasis of medullary thyroid carcinoma investigated by transscleral fine-needle aspiration. A case report and review of the literature.

Diagn Cytopathol 2018 Sep 16;46(9):764-768. Epub 2018 Apr 16.

Department of Pathology, Institut Curie, Paris, France.

Medullary thyroid carcinoma occurs in a sporadic setting and may also be inherited in an autosomal dominant fashion, which is related with germline mutations of the RET gene. Metastases are often present at the time of a diagnosis-most frequently within the cervical lymph nodes, followed by the liver, lungs, and bones. Intraocular metastases are extremely rare. Read More

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http://doi.wiley.com/10.1002/dc.23945
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http://dx.doi.org/10.1002/dc.23945DOI Listing
September 2018
7 Reads

BLU-667 Targets RET-Altered Cancers.

Authors:

Cancer Discov 2018 Jun 15;8(6):OF8. Epub 2018 Apr 15.

Findings from a phase I study indicate that the investigational RET inhibitor BLU-667 is safe and well tolerated, inducing good responses in patients with RET-altered medullary thyroid cancer or non-small cell lung cancer. Read More

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http://dx.doi.org/10.1158/2159-8290.CD-NB2018-050DOI Listing
June 2018
2 Reads

Precision Targeted Therapy with BLU-667 for -Driven Cancers.

Cancer Discov 2018 Jul 15;8(7):836-849. Epub 2018 Apr 15.

Blueprint Medicines Corporation, Cambridge, Massachusetts.

The receptor tyrosine kinase rearranged during transfection (RET) is an oncogenic driver activated in multiple cancers, including non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and papillary thyroid cancer. No approved therapies have been designed to target RET; treatment has been limited to multikinase inhibitors (MKI), which can have significant off-target toxicities and limited efficacy. BLU-667 is a highly potent and selective RET inhibitor designed to overcome these limitations. Read More

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http://cancerdiscovery.aacrjournals.org/lookup/doi/10.1158/2
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http://dx.doi.org/10.1158/2159-8290.CD-18-0338DOI Listing
July 2018
44 Reads

Genotype-specific progression of hereditary medullary thyroid cancer.

Hum Mutat 2018 06 3;39(6):860-869. Epub 2018 May 3.

Medical Faculty, Department of General, Visceral and Vascular Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

Although already 25 years into the genomic era, age-related progression of hereditary medullary thyroid cancer (MTC), the prevalence of which is estimated at one in 80,000 inhabitants, remains to be delineated for most unique RET (REarranged during Transfection) mutations. Included in this study were 567 RET carriers. The age-related progression of MTC across histopathological groups (normal thyroid/C-cell hyperplasia; node-negative MTC; node-positive MTC) was statistically significant for 13 unique RET mutations (p. Read More

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http://dx.doi.org/10.1002/humu.23430DOI Listing
June 2018
7 Reads

Clinical significance of RET and RAS mutations in sporadic medullary thyroid carcinoma: a meta-analysis.

Endocr Relat Cancer 2018 06 3;25(6):633-641. Epub 2018 Apr 3.

Department of PathologyUniversity of Yamanashi, Chuo, Yamanashi, Japan

There are ongoing debates with respect to the prognostic roles of molecular biomarkers in sporadic medullary thyroid carcinoma (MTC). In this study, we aimed at investigating the prognostic value of and mutations - the two most common mutations in sporadic MTCs. A search was conducted in four electronic databases. Read More

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http://dx.doi.org/10.1530/ERC-18-0056DOI Listing
June 2018
12 Reads

p.Val804Met, the Most Frequent Pathogenic Mutation in RET, Confers a Very Low Lifetime Risk of Medullary Thyroid Cancer.

J Clin Endocrinol Metab 2018 Nov;103(11):4275-4282

Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.

Context: To date, penetrance figures for medullary thyroid cancer (MTC) for variants in rearranged during transfection (RET) have been estimated from families ascertained because of the presence of MTC.

Objective: To gain estimates of penetrance, unbiased by ascertainment, we analyzed 61 RET mutations assigned as disease causing by the American Thyroid Association (ATA) in population whole-exome sequencing data.

Design: For the 61 RET mutations, we used analyses of the observed allele frequencies in ∼51,000 individuals from the Exome Aggregation Consortium (ExAC) database that were not contributed via The Cancer Genome Atlas (TCGA; non-TCGA ExAC), assuming lifetime penetrance for MTC of 90%, 50%, and unbounded. Read More

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https://academic.oup.com/jcem/article/103/11/4275/4951497
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http://dx.doi.org/10.1210/jc.2017-02529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194854PMC
November 2018
11 Reads

Outcome of Treatment for Medullary Thyroid Carcinoma-a Single Centre Experience.

Indian J Surg Oncol 2018 Mar 8;9(1):52-58. Epub 2017 Dec 8.

1Department of Endocrine Surgery, Christian Medical College and Hospital, Paul Brand building (1205), Vellore, Tamil Nadu India.

We conducted this study to evaluate the demography, clinical presentation, management and outcomes of medullary thyroid carcinoma (MTC) from the Indian context. This was a retrospective study of patients with MTC managed between January 2008 and December 2016. All pertinent data was collected and the results were analysed using STATA (v. Read More

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http://link.springer.com/10.1007/s13193-017-0718-2
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http://dx.doi.org/10.1007/s13193-017-0718-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856701PMC
March 2018
15 Reads

Challenging clinically unresponsive medullary thyroid cancer: Discovery and pharmacological activity of novel RET inhibitors.

Eur J Med Chem 2018 Apr 2;150:491-505. Epub 2018 Mar 2.

Dipartimento di Farmacia, Università di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy. Electronic address:

It is now known that "gain of function" mutations of RET (REarranged during Transfection) kinase are specific and key oncogenic events in the onset of thyroid gland cancers such as the Medullary Thyroid Carcinoma (MTC). Although a number of RET inhibitors exist and are capable of inhibiting RET variants, in which mutations are outside the enzyme active site, the majority becomes dramatically ineffective when mutations are within the protein active site (V804L and V804M). Pursuing a receptor-based virtual screening against the kinase domain of RET, we found that compound 5 is able to inhibit efficiently both wild type and V804L mutant RET. Read More

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http://dx.doi.org/10.1016/j.ejmech.2018.02.080DOI Listing
April 2018
14 Reads

Prostate adenocarcinoma in a young patient with multiple endocrine neoplasia 2B.

Ann Endocrinol (Paris) 2018 Apr 9;79(2):86-89. Epub 2018 Mar 9.

Service d'endocrinologie, diabétologie et maladies métaboliques, CHU Clermont-Ferrand, 58, rue Montalembert, 63003 Clermont-Ferrand, France; UMR CNRS 6293, Inserm U1103, département génétique reproduction et développement, université Clermont-Auvergne, BP 10448, 63177 Aubiere, France.

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http://dx.doi.org/10.1016/j.ando.2017.09.002DOI Listing
April 2018
7 Reads

Medullary thyroid cancer, leukemia, mesothelioma and meningioma associated with germline APC and RASAL1 variants: a new syndrome?

Hormones (Athens) 2017 Oct;16(4):423-428

1st Department of Internal Medicine, Laiko Hospital, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str., Goudi, 11527, Athens, Greece.

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor hereditary in 35% of cases. The most common syndromic form is in the context of the multiple endocrine neoplasia type 2 (MEN 2) syndromes in association with other tumors and due to germline RET mutations. We describe a 57-year-old female patient diagnosed with sporadic MTC. Read More

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http://dx.doi.org/10.14310/horm.2002.1763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341468PMC
October 2017
19 Reads

RET mutation heterogeneity in primary advanced medullary thyroid cancers and their metastases.

Oncotarget 2018 Feb 4;9(11):9875-9884. Epub 2018 Jan 4.

Endocrine Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy.

Purpose: Medullary Thyroid Cancer (MTC) whose pathogenesis is strictly related to proto-oncogene alterations, has been shown to have a heterogenic mutation profile in subpopulations of MTC. The aim of our study was to investigate the somatic mutation profile in primary MTC and in the corresponding metastatic tissues in a series of advanced metastatic cases.

Results: This study demonstrated that in about 20% of cases a different mutation profile can be found when comparing primary tumor and its corresponding metastases. Read More

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http://dx.doi.org/10.18632/oncotarget.23986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839408PMC
February 2018
15 Reads

Medullary Thyroid Carcinoma: Survival Analysis and Evaluation of Mutation-Specific Immunohistochemistry in Detection of Sporadic Disease.

World J Surg 2018 05;42(5):1432-1439

University of Sydney Endocrine Surgical Unit, Suite 202, AMA House, 69 Christie St, St Leonards, Sydney, NSW, 2065, Australia.

Introduction: Medullary thyroid cancer (MTC) is a rare tumour of neuroendocrine origin with a more aggressive profile than differentiated thyroid cancer. Familial cases of MTC are associated with RET mutations whilst RAS mutations appear to be a frequent finding in RET negative tumours. The aims of this study were to analyse survival outcomes in MTC and to evaluate the role of RAS immunohistochemistry in the identification of sporadic disease. Read More

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http://dx.doi.org/10.1007/s00268-018-4551-8DOI Listing
May 2018
6 Reads