rdf:type |
|
lifeskim:mentions |
umls-concept:C0006826,
umls-concept:C0017262,
umls-concept:C0021920,
umls-concept:C0026882,
umls-concept:C0086418,
umls-concept:C0185117,
umls-concept:C0205225,
umls-concept:C0205263,
umls-concept:C0205341,
umls-concept:C0221099,
umls-concept:C0920269,
umls-concept:C1417250,
umls-concept:C2911684
|
pubmed:issue |
15
|
pubmed:dateCreated |
2004-4-8
|
pubmed:abstractText |
Frequent mutations of coding nucleotide repeats are thought to contribute significantly to carcinogenesis associated with microsatellite instability (MSI). We have shown that shortening of the poly(T)11 within the polypyrimidine stretch/accessory splicing signal of human MRE11 leads to the reduced expression and functional impairment of the MRE11/NBS1/RAD50 complex. This mutation was selectively found in mismatch repair (MMR) defective cell lines and potentially identifies MRE11 as a novel target for MSI. Here, we examined 70 microsatellite unstable primary human cancers and we report that MRE11 mutations occur in 83.7 and 50% of the colorectal and endometrial cancers, respectively. In the colorectal cancer series, mutated MRE11 is more frequently associated with advanced age at diagnosis and A/B stages. Biallelic mutations were present in 38.8% of the cases and more frequently associated with lower (G1/G2) grade tumors. Impaired MRE11 expression was prevalent in primary colorectal tumors with larger and biallelic shortening of the poly(T)11. Immunohistochemistry confirmed the impaired MRE11 expression and revealed NBS1-defective expression in MRE11 mutated cancers. Together with the observation that perturbation of the MRE11/NBS1/RAD50 complex predisposes to cancer, our work highlights MRE11 as a new common target in the MMR deficient tumorigenesis and suggests its role in colorectal carcinogenesis.
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pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Endodeoxyribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/Exodeoxyribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/MRE11 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/NBN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RAD50 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
|
pubmed:issn |
0950-9232
|
pubmed:author |
pubmed-author:AmbrosiniMaria IreneMI,
pubmed-author:BerniSilviaS,
pubmed-author:BidoliEttoreE,
pubmed-author:CerignoliFabioF,
pubmed-author:D'AmatiGiuliaG,
pubmed-author:FratiLuigiL,
pubmed-author:GianniniGiuseppeG,
pubmed-author:GulinoAlbertoA,
pubmed-author:RinaldiChristianC,
pubmed-author:RistoriElisabettaE,
pubmed-author:ScambiaGiovanniG,
pubmed-author:ScrepantiIsabellaI,
pubmed-author:VielAlessandraA
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pubmed:issnType |
Print
|
pubmed:day |
8
|
pubmed:volume |
23
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
2640-7
|
pubmed:dateRevised |
2007-5-10
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pubmed:meshHeading |
pubmed-meshheading:15048091-Aged,
pubmed-meshheading:15048091-Alleles,
pubmed-meshheading:15048091-Base Pair Mismatch,
pubmed-meshheading:15048091-Cell Cycle Proteins,
pubmed-meshheading:15048091-Cell Line,
pubmed-meshheading:15048091-Colorectal Neoplasms,
pubmed-meshheading:15048091-DNA Repair,
pubmed-meshheading:15048091-DNA Sequence, Unstable,
pubmed-meshheading:15048091-DNA-Binding Proteins,
pubmed-meshheading:15048091-Endodeoxyribonucleases,
pubmed-meshheading:15048091-Exodeoxyribonucleases,
pubmed-meshheading:15048091-Exons,
pubmed-meshheading:15048091-Female,
pubmed-meshheading:15048091-Humans,
pubmed-meshheading:15048091-Immunohistochemistry,
pubmed-meshheading:15048091-Introns,
pubmed-meshheading:15048091-Male,
pubmed-meshheading:15048091-Microsatellite Repeats,
pubmed-meshheading:15048091-Middle Aged,
pubmed-meshheading:15048091-Mutation,
pubmed-meshheading:15048091-Neoplasms,
pubmed-meshheading:15048091-Nuclear Proteins,
pubmed-meshheading:15048091-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:15048091-Tumor Cells, Cultured
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pubmed:year |
2004
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pubmed:articleTitle |
Mutations of an intronic repeat induce impaired MRE11 expression in primary human cancer with microsatellite instability.
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pubmed:affiliation |
Department of Experimental Medicine and Pathology, University La Sapienza, Policlinico Umberto I, Viale Regina Elena, 324, 00161 Rome, Italy. guiseppe.giannini@uniroma1.it
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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