Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours

1994 ◽  
Vol 3 (2) ◽  
pp. 237-241 ◽  
Author(s):  
Charis Eng ◽  
Darrin P. SmIth ◽  
Lois M. MullIgan ◽  
Maria A. Nagal ◽  
Catherine S. Healey ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Point Mutation ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

scholarly journals A mutation in the RET proto-oncogene in Hirschsprung's disease affects the tyrosine kinase activity associated with multiple endocrine neoplasia type 2A and 2B

1996 ◽  
Vol 314 (2) ◽  
pp. 397-400 ◽  
Author(s):  
Maria Pia COSMA ◽  
Luigi PANARIELLO ◽  
Loredana QUADRO ◽  
Nina A. DATHAN ◽  
Olimpia FATTORUSO ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Tyrosine Kinase Domain ◽  
Cos Cells ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

We demonstrate that a Hirschsprung (HSCR) mutation in the tyrosine kinase domain of the RET proto-oncogene abolishes in cis the tyrosine-phosphorylation associated with the activating mutation in multiple endocrine neoplasia type 2A (MEN2A) in transiently transfected Cos cells. Yet the double mutant RET2AHS retains the ability to form stable dimers, thus dissociating the dimerization from the phosphorylation potential. Co-transfection experiments with single and double mutants carrying plasmids RET2A and RET2AHS in different ratios drastically reduced the phosphorylation levels of the RET2A protein, suggesting a dominant-negative effect of the HSCR mutation. Also, the phosphorylation associated with the multiple endocrine neoplasia type 2B (MEN2B) allele was affected in experiments with single and double mutants carrying plasmids co-transfected under the same conditions. Finally, analysis of the enzymic activity of MEN2A and MEN2B tumours confirmed the relative levels of tyrosine phosphorylation observed in Cos cells, indicating that this condition, in vivo, may account for the RET transforming potential.

Update on the Treatment of Medullary Thyroid Carcinoma in Patients with Multiple Endocrine Neoplasia Type 2

2020 ◽  
Vol 52 (08) ◽  
pp. 588-597 ◽  
Author(s):  
Maran Ilanchezhian ◽  
Sophia Khan ◽  
Christian Okafor ◽  
John Glod ◽  
Jaydira Del Rivero
Keyword(s):  
Thyroid Carcinoma ◽  
Tyrosine Kinase ◽  
Medullary Thyroid Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Multiple Endocrine Neoplasia ◽  
Kinase Inhibitors ◽  
Multiple Endocrine Neoplasia Type ◽  
Medullary Thyroid ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

AbstractMedullary Thyroid Carcinoma (MTC) is a rare neuroendocrine cancer that accounts for 1–2% of thyroid cancers in the United States (U.S.). While most cases are sporadic, 25% of MTC cases are hereditary. These hereditary cases occur in the setting of Multiple Endocrine Neoplasia Type 2A (MEN2A) or 2B (MEN2B) driven by mutations in the Rearranged during Transfection RET proto-oncogene. This article discusses hereditary MTC in the setting of MEN2 and the treatment options available for it. The first line treatment for this disease is typically a total thyroidectomy and tyrosine kinase inhibitors. Two tyrosine kinase inhibitors, vandetanib and cabozantinib, have been approved for treatment of advanced MTC, but options beyond those are limited. However, several promising treatments are being studied, which are discussed in this review.

scholarly journals Analysis of RET Gene Point Mutation with Multiple Endocrine Neoplasia Type 2B

2007 ◽  
Vol 18 (1) ◽  
pp. 79-85
Author(s):  
Sung Won Kim ◽  
Bong Ju Lee ◽  
Joo Yeun Kim ◽  
Kang Dae Lee ◽  
Byung Joo Lee ◽  
...  
Keyword(s):  
Point Mutation ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Ret Gene ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

scholarly journals Structure and function of RET in multiple endocrine neoplasia type 2

2018 ◽  
Vol 25 (2) ◽  
pp. T79-T90 ◽  
Author(s):  
Iván Plaza-Menacho
Keyword(s):  
Cell Biology ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Structure And Function ◽  
Tyrosine Kinase Domain ◽  
Cancer Syndrome ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
And Function

It has been twenty-five years since the discovery of oncogenic germline RET mutations as the cause of multiple endocrine neoplasia type 2 (MEN2). Intensive work over the last two and a half decades on RET genetics, signaling and cell biology has provided the current bases for the genotype–phenotype and functional correlations within this cancer syndrome. On the contrary, the structural and molecular basis for RET tyrosine kinase domain activation and oncogenic deregulation has remained largely elusive. Recent studies with a strong crystallographic and biochemical focus have started to elucidate key insights into such molecular and atomic details revealing unexpected and private mechanisms of actions and molecular determinants not previously envisioned. This review focuses on the structure and function of the RET receptor, and in particular, on what a more detailed view of the protein itself and what the current structural and molecular information tell us about the genotype and phenotype relationships in the cancer syndrome MEN2.

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