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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1996-11-20
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pubmed:abstractText |
Multiple endocrine neoplasia type 2 [MEN 2] is an autosomal dominant cancer syndrome with two subtypes, 2A and 2B. MEN 2A and medullary thyroid cancer [MTC] are caused by > 25 different point mutations in exons 10, 11, and 13 of the RET proto-oncogene, whereas MEN 2B is caused by a single exon 16-point mutation. Various molecular methods have been used to identify the different mutations, including DNA sequencing, restriction enzymatic analyses, chemical cleavage mismatch, Single Stranded Conformational Polymorphism [SSCP], and Denaturing Gradient Gel Electrophoresis [DGGE]. These techniques, although useful and accurate, are labor intensive and some involve the use of radioactivity. We have developed a multiplex PCR assay simultaneously to amplify exons 10, 11, and 13 of the RET proto-oncogene. The multiplex PCR product is then analyzed on a modified Mutation Detection Enhancement [MDE] matrix for heteroduplex identification and visualized with ethidium bromide. Distinct heteroduplexes were detected for each known RET proto-oncogene mutation available in our laboratory (nine in exon 10, five in exon 11, one in exon 13, and the single exon 16 mutation). Presymptomatic DNA diagnosis of MEN 2 is essential since pentagastrin-stimulated calcitonin studies can occasionally produce false positive results and lead to unnecessary thyroidectomies. Prophylactic thyroidectomy is recommended by age 5 or 6 once a mutation is identified in a patient, since penetrance is very high. MDE heteroduplex detection provides a quick, efficient, and inexpensive method of screening for RET mutations in MTC patients with unknown mutations, or for presymptomatic diagnosis in individuals at risk for inheriting a known RET mutation. Confirmation of the specific mutation can be achieved by restriction enzymatic digestion (if feasible) or by DNA sequencing.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleic Acid Heteroduplexes,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-ret,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ret oncogene protein, Drosophila
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pubmed:status |
MEDLINE
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pubmed:issn |
1059-7794
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
64-70
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8807338-Carcinoma, Medullary,
pubmed-meshheading:8807338-Drosophila Proteins,
pubmed-meshheading:8807338-Humans,
pubmed-meshheading:8807338-Multiple Endocrine Neoplasia Type 2a,
pubmed-meshheading:8807338-Multiple Endocrine Neoplasia Type 2b,
pubmed-meshheading:8807338-Mutation,
pubmed-meshheading:8807338-Nucleic Acid Heteroduplexes,
pubmed-meshheading:8807338-Polymerase Chain Reaction,
pubmed-meshheading:8807338-Polymorphism, Single-Stranded Conformational,
pubmed-meshheading:8807338-Proto-Oncogene Proteins,
pubmed-meshheading:8807338-Proto-Oncogene Proteins c-ret,
pubmed-meshheading:8807338-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:8807338-Thyroid Neoplasms
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pubmed:year |
1996
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pubmed:articleTitle |
Diagnosis of multiple endocrine neoplasia [MEN] 2A, 2B and familial medullary thyroid cancer [FMTC] by multiplex PCR and heteroduplex analyses of RET proto-oncogene mutations.
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pubmed:affiliation |
Medical Genetics and Birth Defects Center, Henry Ford Hospital, Detroit, Michigan 48202-2689, USA.
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pubmed:publicationType |
Journal Article
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