Utilize este identificador para referenciar este registo: https://hdl.handle.net/1822/58157

TítuloEvaluation of MLH1 variants of unclear significance
Autor(es)Köger, Nicole
Paulsen, Lea
López-Kostner, Francisco
Della Valle, Adriana
Vaccaro, Carlos Alberto
Palmero, Edenir Inêz
Alvarez, Karin
Sarroca, Carlos
Neffa, Florencia
Kalfayan, Pablo German
Gonzalez, Maria Laura
Rossi, Benedito Mauro
Reis, R. M.
Brieger, Angela
Zeuzem, Stefan
Hinrichsen, Inga
Dominguez-Valentin, Mev
Plotz, Guido
Palavras-chaveColorectal Neoplasms, Hereditary Nonpolyposis
Computer Simulation
HEK293 Cells
Humans
Middle Aged
MutL Protein Homolog 1
Protein Conformation
South America
Genetic Predisposition to Disease
Mutation
classification
Lynch syndrome
mlh1
pathogenicity
variant of uncertain significance
DataJul-2018
EditoraWiley
RevistaGenes Chromosomes and Cancer
CitaçãoKöger, N., Paulsen, L., López‐Kostner, F., Della Valle, A., et. al. (2018) Evaluation of MLH1 variants of unclear significance. Genes, Chromosomes and Cancer, 57(7), 350-358
Resumo(s)Inactivating mutations in the MLH1 gene cause the cancer predisposition Lynch syndrome, but for small coding genetic variants it is mostly unclear if they are inactivating or not. Nine such MLH1 variants have been identified in South American colorectal cancer (CRC) patients (p.Tyr97Asp, p.His112Gln, p.Pro141Ala, p.Arg265Pro, p.Asn338Ser, p.Ile501del, p.Arg575Lys, p.Lys618del, p.Leu676Pro), and evidence of pathogenicity or neutrality was not available for the majority of these variants. We therefore performed biochemical laboratory testing of the variant proteins and compared the results to protein in silico predictions on structure and conservation. Additionally, we collected all available clinical information of the families to come to a conclusion concerning their pathogenic potential and facilitate clinical diagnosis in the affected families. We provide evidence that four of the alterations are causative for Lynch syndrome, four are likely neutral and one shows compromised activity which can currently not be classified with respect to its pathogenic potential. The work demonstrates that biochemical testing, corroborated by congruent evolutionary and structural information, can serve to reliably classify uncertain variants when other data are insufficient.
TipoArtigo
URIhttps://hdl.handle.net/1822/58157
DOI10.1002/gcc.22536
ISSN1045-2257
e-ISSN1098-2264
Versão da editorahttps://onlinelibrary.wiley.com/doi/full/10.1002/gcc.22536
Arbitragem científicayes
AcessoAcesso aberto
Aparece nas coleções:ICVS - Artigos em revistas internacionais / Papers in international journals

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