RGD Reference Report - Microsatellite instability and mutation analysis of candidate genes in urothelial cell carcinomas of upper urinary tract. - Rat Genome Database

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Microsatellite instability and mutation analysis of candidate genes in urothelial cell carcinomas of upper urinary tract.

Authors: Mongiat-Artus, P  Miquel, C  Van der Aa, M  Buhard, O  Hamelin, R  Soliman, H  Bangma, C  Janin, A  Teillac, P  Van der Kwast, T  Praz, F 
Citation: Mongiat-Artus P, etal., Oncogene. 2006 Mar 30;25(14):2113-8.
RGD ID: 2293511
Pubmed: PMID:16288216   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.onc.1209229   (Journal Full-text)

A subset of upper urinary tract urothelial cell carcinomas (UUC), arising sporadically or as a manifestation of hereditary non-polyposis colorectal cancer, displays microsatellite instability (MSI). MSI tumours are characterized by defective mismatch repair and accumulation of frameshift mutations in numerous genes harbouring repeats in their coding sequences. We have evaluated the incidence of MSI in UUC and the intratumoral distribution of mutations in 13 candidate target genes. A total of 58 unselected UUC were screened for MSI using the panel of five mononucleotide markers recently recommended by the National Cancer Institute for a precise MSI assessment. Four tumours displayed MSI (7%), among which at least three had alterations in the genes MSH3, BAX, MRE11, RAD50. Mutations in genes involved in key cellular pathways (ATR, DNA-PKcs, MBD4, TCF-4, MSH6, and BLM) were further detected. BAX and MRE11 mutations tend to present homogeneously within the three MSI UUC. Immunohistochemistry (MLH1, MSH2, MSH6) showed that loss of mismatch repair protein expression occurred in all MSI UUC defining the gene defect and that MRE11 and RAD50 mutations were associated with their concomitant loss expression. In conclusion, MSI UUC represent a small proportion of UUC in which BAX and MRE11 mutations are frequent and may play a role early in UUC tumorigenesis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RAD50Humantransitional cell carcinoma  IAGP upper urinary tract urothelial cell carcinoma and DNA:mutation:tumor:associated with microsatellite instabilityRGD 
Rad50Rattransitional cell carcinoma  ISORAD50 (Homo sapiens) RGD 
Rad50Mousetransitional cell carcinoma  ISORAD50 (Homo sapiens) RGD 
MSH2HumanUrogenital Neoplasms  IEP protein:decreased expressionRGD 
MSH6HumanUrogenital Neoplasms  IDA DNA more ...RGD 
Msh2RatUrogenital Neoplasms  ISOMSH2 (Homo sapiens)protein:decreased expressionRGD 
Msh2MouseUrogenital Neoplasms  ISOMSH2 (Homo sapiens)protein:decreased expressionRGD 
Msh6MouseUrogenital Neoplasms  ISOMSH6 (Homo sapiens)DNA more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Msh2  (mutS homolog 2)
Rad50  (RAD50 double strand break repair protein)

Genes (Mus musculus)
Msh2  (mutS homolog 2)
Msh6  (mutS homolog 6)
Rad50  (RAD50 double strand break repair protein)

Genes (Homo sapiens)
MSH2  (mutS homolog 2)
MSH6  (mutS homolog 6)
RAD50  (RAD50 double strand break repair protein)


Additional Information