Recombinant Human Proto-oncogene tyrosine-protein kinase receptor Ret (RET), partial (Active)

1. mutation was found in 23.8% of hereditary medullary thyroid carcinoma patients tested; most commonly mutated codon was codon 634 (37.1%), followed by codon 918 (14.3%) PMID: 29779869
2. Novel low frequency SNP in ERT locus is associated with Hirschsprung disease. PMID: 29379196
3. RET alterations, such as RET-oncogene fusions, are present in a subset of breast cancers, and are promising therapeutic targets. PMID: 30446652
4. RET gene alterations (copy number gain and rearrangement) exist in all RET-positive samples. RET-positive expression is a relatively independent factor in non-small cell lung cancer cases(NSCLC) patients, which indicates that the RET gene may be a novel target site for personalized treatment of NSCLC. PMID: 29473341
5. Somatic mutations of the RET gene are underrecognized in HSCR. Molecular investigation of the parents of patients with seemingly sporadic mutations is essential to determine recurrence risk in these families. PMID: 29261189
6. in vitro transactivation of the RET promoter by different Hirschsprung disease-associated PHOX2B polyA variants has resulted significantly lower compared to the effect of PHOX2B wild type protein. PMID: 28433712
7. These results support the association between genetic variation of RET and NRG1 and susceptibility to Hirschsprung disease in the Chinese population. PMID: 28256518
8. the results from three transcriptome-based platforms (Nanostring Elements, Agena LungFusion panel and ThermoFisher NGS fusion panel) were compared to those obtained from ALK, ROS1 and RET Fluorescence In Situ Hybridization on 51 clinical specimens. PMID: 28181564
9. The authors found a significant association between the localization of RET mutations and the expression of three genes: NNAT (suggested to be a tumour suppressor gene), CDC14B (involved in cell cycle control) and NTRK3 (tyrosine receptor kinase that undergoes rearrangement in papillary thyroid cancer) in patients with medullary thyroid cancer. PMID: 28181547
10. the inverse relationship between GFRalpha1 and C-Ret, as knocking down C-Ret led to increases in GFRalpha1 expression. PMID: 29018141
11. Rare synonymous changes in the RET gene, c.1827C>T (p.Cys609Cys), c.2364C>T (p.Ile788Ile), and c.2673G>A (p.Ser891Ser), were identified in medullary thyroid carcinoma patients and c.2418C>T (p.Tyr806Tyr) in a patient suspected of MEN2 syndrome PMID: 28647780
12. RET rearrangement is associated with lung adenocarcinoma. PMID: 29549897
13. The data suggest that all families with the C611Y germline mutation in Denmark originate from a recent common ancestor, probably explaining the unusually high prevalence of this mutation in Multiple Endocrine Neoplasia 2A families. PMID: 29020875
14. Our results demonstrated greater expression of pRET and CXCR4 in cisplatinresistant neuroblastomas (NBs). Vandetanib significantly inhibited SHSY5YR cell proliferation, colony formation, and invasion, while downregulating pRET and CXCR4 expression PMID: 29436676
15. LRIG1 is a negative regulator of RET2A and RET2B and is also downregulated in papillary and medullary thyroid carcinoma PMID: 29436694
16. Study in SK-N-MC cells found that C634R mutation could enhance RET protein expression and change the location of the mutated protein and forced it into the nucleus. PMID: 29237911
17. The frequencies of ALK, ROS1 and RET rearrangements are low in non-adenocarcinoma NSCLC patients. And their clinical characteristics are similar to those in lung adenocarcinoma. Fusions of the above 3 genes are not prognostic factor for non-adnocarcinoma NSCLC patients. PMID: 27635639
18. BRAFV600E and RET/PTC and the expression of NF-kappaB promote the proliferation and migration of papillary thyroid carcinoma cells in vitro. PMID: 29117154
19. The RET proto-oncogene located on chromosome 10q11.2 encodes a 1114-amino acid transmembrane receptor with a cadherin-related motif and a cysteine-rich domain in the extracellular domain. PMID: 28799054
20. We found 6 single nucleotide polymorphisms in RET that were independent contributors to Hischsprung disease PMID: 28930629
21. data establish differences in the mechanisms of RET9 and RET51 ubiquitylation and internalization that may influence the strength and duration of RET isoform signals and cellular outputs. PMID: 28794017
22. Study demonstrate that the kinesin and kinase domains of KIF5B-RET act together to establish an emergent microtubule and RAB-vesicle-dependent RET-SRC-EGFR-FGFR signaling hub. Study demonstrate that drugs designed to inhibit RET alone work poorly in KIF5B-RET-transformed cells. PMID: 28877471
23. RET knockdown significantly decreased xenografts tumor growth in vivo, confirming the oncogenic impact of RET signaling in vivo. PMID: 28490466
24. Each of these autosomal dominant syndromes results from a specific germline mutation in unique genes: MEN1 is due to pathogenic MEN1 variants (11q13), MEN2A and MEN2B are due to pathogenic RET variants (10q11.21), MEN4 is due to pathogenic CDKN1B variants (12p13.1), and the HPT-JT syndrome is due to pathogenic CDC73 variants (1q25). PMID: 28674121
25. RET p.C634F mutation is associated with Multiple Endocrine Neoplasia Type 2A with Cutaneous Lichen Amyloidosis. PMID: 29420094
26. These data support the inclusion of patients bearing RET alterations in ongoing and future molecularly enriched clinical trials to explore RXDX-105 efficacy across a variety of tumor types. PMID: 28011461
27. These results implicate EGFR as a key regulator of RET activation in A+AD and suggest that EGFR inhibitors may be therapeutic in patients with A+AD tumors even in the absence of an EGFR or RET mutation. PMID: 28460442
28. In a cohort of MEN 2 families, the distribution of RET mutations in Denmark appears to differ from that of other populations. Mutations in codon 611 were the most prevalent, followed by more frequently reported mutations. This might be due to a possible founder effect for the p.C611Y mutation. PMID: 27809725
29. RET inhibitors could both impair primary tumor growth and tumor dissemination, thereby providing a potential therapeutic advantage when used in combination with aromatase inhibitors in postmenopausal ER+ breast cancers. PMID: 27602955
30. exposure of medullary thyroid cancer cells to a tri-substituted naphthalene diimide resulted in a significant antiproliferative activity paralleled by inhibition of RET expression PMID: 27351133
31. Our data show that RET expression promotes a more mesenchymal phenotype with reduced cell-cell adhesion and increased invasiveness in papillary thyroid carcinoma cell models, but is more important for tumour cell survival, proliferation and anoikis resistance in medullary thyroid carcinoma models. Our data suggest that the RET51 isoform plays a more prominent role in mediating these processes compared to RET9. PMID: 27872141
32. From this case series, the largest such experience to date, it is concluded that the RET(K666N) variant is likely pathogenic and associated with low penetrance of medullary thyroid carcinoma. PMID: 27673361
33. Multilayer OMIC data analysis uncovered methylation hallmarks in genetically defined Medullary thyroid carcinoma (MTC) and revealed JAK/Stat signaling effector STAT3 as a potential therapeutic target for the treatment of RET(M918T) MTCs PMID: 27620278
34. DNA mutational analysis of RET germline mutations associated with medullary thyroid carcinoma in a Druze family. PMID: 28688347
35. increased overall survival was observed in breast cancer patients who are carriers of the variant allele of SNP rs2435357 PMID: 27034161
36. These data suggest that angiogenesis in RET mutation medullary thyroid carcinomas may be more intense and complete than that found in RETwt tumors, a feature that might increase their susceptibility to antiangiogenic therapy. PMID: 27402614
37. Significant genetic risk for Hirschsprung disease (HSCR) was imparted by rs2435357 and rs2506030 at RET and by rs12707682 at SEMA3 in a Chinese population. No evidence was found of a genetic association between HSCR and either of the NRG1 SNPs rs7835688 and rs16879552, at either allele or genotype level. PMID: 27203398
38. Durable benefits with pemetrexed-based therapies in RET-rearranged lung cancers are comparable with ALK- and ROS1-rearranged lung cancers. When selecting therapies for patients with RET-rearranged lung cancers, pemetrexed-containing regimens should be considered. PMID: 27056998
39. Data suggest that the KIAA1217-RET-fusion gene is a promising target for lung cancer treatment. PMID: 27150058
40. The RET M918V mutation is co-segregating in 8 familial MTC kindreds with validated evidence of a founder effect. PMID: 27807060
41. Mutational analysis in 17 cases of Medullary thyroid carcinoma, the somatic missense mutation at codon 918 of RET was found in 2 of the 17 Medullary thyroid carcinoma(MTC)s, and one case presented MEN2 phenotype including MTC. PMID: 28166591
42. study provided useful information on RET variants that should be subjected to further study PMID: 29131865
43. Review of RET mutations and mechanisms in medullary thyroid cancer. PMID: 26678667
44. The cardiac GFRA2 signaling pathway is distinct from the canonical pathway dependent on the RET tyrosine kinase. PMID: 27396331
45. identified four genomic rearrangements involving the genes BRAF, RET, and ROS1 PMID: 27864876
46. Detection of Gene Rearrangements in Circulating Tumor Cells: Examples of ALK-, ROS1-, RET-Rearrangements in Non-Small-Cell Lung Cancer and ERG-Rearrangements in Prostate Cancer.( PMID: 28560674
47. These findings support the role of RET in the development of the enteric nervous system but underline the importance of other genetic or environmental factors contributing to the gastrointestinal phenotype of the disease. Somehow, this RET R114H mutation proved to have a role in the etiology of both CIPO and HSCR and could contribute to a more diffuse imbalance of gut dysmotility. PMID: 27273837
48. High RET expression is associated with perineurial invasion of pancreatic adenocarcinoma. PMID: 28092668
49. RET expression was significantly greater in patients with Extraskeletal myxoid chondrosarcoma relative to other types of sarcomas except for liposarcoma PMID: 28423517
50. RET gene rearrangement plays a role in the pathogenesis of papillary thyroid cancer. PMID: 28911147

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HGNC: 9967

OMIM: 114500

KEGG: hsa:5979

STRING: 9606.ENSP00000347942

UniGene: Hs.350321