Utilize este identificador para referenciar este registo: https://hdl.handle.net/1822/67642

TítuloAnalysis of microsatellite instability in medulloblastoma
Autor(es)Pereira, Marta Sofia Carvalho Ribeiro Viana
Almeida, Inês
Sousa, Sónia
Mahler-Araújo, Bethânia
Seruca, Raquel
Pimentel, José
Reis, R. M.
Palavras-chaveAdolescent
Adult
Aged
Biomarkers, Tumor
Cerebellar Neoplasms
Child
Child, Preschool
DNA Methylation
DNA Mutational Analysis
Female
Humans
Immunohistochemistry
Infant
Male
Medulloblastoma
Middle Aged
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Young Adult
Microsatellite Instability
Mismatch repair
Target genes
DataOut-2009
EditoraOxford University Press
RevistaNeuro-Oncology
Resumo(s)Medulloblastoma is the most common malignant brain tumor in children. The presence of microsatellite instability (MSI) in brain tumors, particularly medulloblastomas, has not been properly addressed. The aim of the present study was to evaluate the role of MSI in medulloblastoma carcinogenesis. MSI status was determined in 36 patients using a pentaplex PCR of quasimonomorphic markers (NR27, NR21, NR24, BAT25, and BAT26). Methylation status of mismatch repair (MMR) genes was achieved by methylation-specific multiplex ligation-dependent probe amplification (MLPA). In addition, MutS homolog 6 (MSH6) expression was determined by immunohistochemistry. Mutations of 10 MSI target genes (TCF4, XRCC2, MBD4, MRE11, ATR, MSH3, TGFBR2, RAD50, MSH6, and BAX) were studied by pentaplex PCR followed by analysis with GeneScan 3.7 software. Mutation analysis of hotspot regions of beta-catenin (CTNNB1) and BRAF (v-raf murine sarcoma viral oncogene homolog B1) oncogenes was performed by PCR single-strand conformation polymorphism analysis followed by direct sequencing. Among the 36 tumors, we found four (11%) cases with instability, one with high MSI and three with low MSI. Methylation analysis of MMR genes in cases presenting shifts on the MSI markers revealed mild hypermethylation of MSH6 in 75% of cases, yet MSH6 was expressed in all the tumors. The MSI target genes MBD4 (methyl-CpG binding domain protein 4) and MRE11 (meiotic recombination 11 homolog A) were mutated in two different tumors. No CTNNB1 or BRAF mutations were found. This study is the most comprehensive analysis of MSI in medulloblastomas to date. We observed the presence of MSI together with mutations of MSI target genes in a small fraction of cases, suggesting a new genetic pathway for a role in medulloblastoma development.
TipoArtigo
URIhttps://hdl.handle.net/1822/67642
DOI10.1215/15228517-2008-115
ISSN1522-8517
e-ISSN1523-5866
Arbitragem científicayes
AcessoAcesso aberto
Aparece nas coleções:ICVS - Artigos em revistas internacionais / Papers in international journals

Ficheiros deste registo:
Ficheiro Descrição TamanhoFormato 
Viana-pereira-2009-Analysis-of-microsatellite-instabil.pdf662,08 kBAdobe PDFVer/Abrir

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID