Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A

@article{Mulligan1993GermlineMO,
  title={Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A},
  author={Lois M. Mulligan and John B. J. Kwok and Catherine S. Healey and M. Elsdon and Charis Eng and Emily Gardner and Donald R. Love and Sara E. Mole and Julie Moore and Laura Papi and Margaret A. Ponder and H{\aa}kan Telenius and Alan Tunnacliffe and Bruce A. J. Ponder},
  journal={Nature},
  year={1993},
  volume={363},
  pages={458-460}
}
MULTIPLE endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytomal. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10qll.2 (refs 2,3). The DNA segment encompasses the RET proto-oncogene, a receptor tyrosine kinase gene expressed in MTC and… 
A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma
TLDR
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TLDR
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TLDR
The observation that the major tissues affected in MEN 2 and Hirschsprung disease have a common origin in the embryonal neural crest, suggest that RET encodes a receptor for a developmental regulator involved in the genesis of a variety of neural crest derivatives, and in the organogenesis of the kidney.
Novel point mutation in exon 10 of the RET proto-oncogene in a family with medullary thyroid carcinoma.
TLDR
A novel RET mutation at codon 611 is reported on in a family with MTC without other clinical manifestations and of rather benign course.
RET Proto-Oncogene and Its Role in Multiple Endocrine Neoplasia and Medullary Thyroid Cancer
The RET proto-oncogene encodes a transmembrane protein receptor tyrosine kinase, the function of which is unknown at present. The inclusion of a discussion of this gene in a book on hormones and
Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC
TLDR
The data show a strong correlation between disease phenotype and the nature and position of theRET mutation, suggesting that a simple, constitutive activation of the RET tyrosine kinase is unlikely to explain the events leading to MEN 2A and FMTC.
Detection of a germline mutation at codon 918 of the RET proto-oncogene in French MEN 2B families
TLDR
Results indicate that a unique mutation at codon 918 of the RET gene is the most prevalent genetic defect causing MEN 2B, but also that rare men 2B cases are associated with different mutations yet to be defined.
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References

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Tight linkage of the ret proto-oncogene with the multiple endocrine neoplasia type 2A locus.
TLDR
The ret proto-oncogene has been mapped to 10q11.2 near the MEN2A locus by in situ hybridization and therefore possibly to be a useful DNA marker for cloning the latter, and a linkage study of Japanese multiple endocrine neoplasia type 2A families using a cosmid clone containing the Ret proto- oncogene as probe suggests this.
The ret proto-oncogene is consistently expressed in human pheochromocytomas and thyroid medullary carcinomas.
TLDR
Since the ret gene has been mapped on chromosome 10, close to the gene which predisposes patients to the MEN2A syndrome, it is suggested that this region of chromosome 10 might be involved in the proliferative and differentiative patterns of these neuroectodermal tissues.
Genetic events in tumour initiation and progression in multiple endocrine neoplasia type 2
TLDR
It is suggested that at least 7 genes contribute to tumour development in MEN 2, including an initiating locus on chromosome 10 and loci on chromosomes 1, 3, 11, 13, 17, and 22 which have a progressional role in these tumours.
Human ret proto-oncogene mapped to chromosome 10q11.2.
TLDR
Using cosmid clones derived from human ret protooncogene as probes, its chromosome localization was determined by fluorescence in situ hybridization and suggested that ret proto-oncogene might be a suitable probe for approaching the MEN2A locus.
Localisation of the gene for multiple endocrine neoplasia type 2A to a 480 kb region in chromosome band 10q11.2.
TLDR
A YAC contig has been constructed spanning 1.1 Mb of human chromosome band 10q11.2 which encompasses three markers closely linked to the gene for MEN 2A, and must include MEN2A, which lies in a 480 kb region between flanking markers D 10S141 and D10S94.
Genetic linkage studies map the multiple endocrine neoplasia type 2 loci to a small interval on chromosome 10q11.2.
We have carried out genetic linkage analyses using fifteen polymorphic loci in the pericentromeric region of chromosome 10 in families with the inherited cancer syndromes multiple endocrine neoplasia
Human trk oncogenes activated by point mutation, in-frame deletion, and duplication of the tyrosine kinase domain
TLDR
The characterization of three in vitro-generated trk oncogenes shows that multiple molecular mechanisms, including point mutation, internal deletion, and kinase domain duplication, can result in the malignant activation of the human trk proto-oncogene.
p53 mutations in colorectal cancer.
TLDR
It is concluded that overexpression of p53 is synonymous with mutation, but some mutations would not be detected by a simple immunohistochemical analysis.
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