title: Frameshift mutations at coding mononucleotide repeat microsatellites in endometrial carcinoma with microsatellite instability.
abstract: BACKGROUND
  Microsatellite instability (MI) is a frequent occurrence in endometrioid carcinoma of the endometrium (EC). Several genes known to contain mononucleotide short tracts in their coding sequences (TGF-beta RII, IGFIIR, BAX, hMSH6, and hMSH3) are likely targets for mutations in these tumors.
  
  
  METHODS
  DNA from 24 patients with EC and MI was extracted from blood and from fresh-frozen and paraffin embedded tumor tissue. Seven of these patients were found to have metastatic spread to paraaortic lymph nodes. DNA also was studied from 10 patients with EC without MI.
  
  
  RESULTS
  Frameshift mutations at coding mononucleotide repeats were detected by single strand conformation polymorphism analysis and DNA sequencing. Frameshift mutations were detected more frequently in BAX (11 of 24 MI positive (+) tumors; 45.8%) than in TGF-beta RII (0 of 24 tumors; 0%), IGFIIR (3 of 24 tumors; 12.5%), hMSH3 (6 of 24 tumors; 25%), or hMSH6 (0 of 24 tumors; 0%). The mutations frequently were distributed heterogeneously throughout the tumors. Overall, frameshift mutations at 1 or more of these mononucleotide repeat microsatellites were found in 17 of 24 MI+ tumors (70.8%) but in none of the 10 MI negative neoplasms. In the seven EC patients with lymph node metastases, mutations in IGFRII were found more commonly in those with metastatic (three of seven patients) rather than primary (one of seven) tumors.
  
  
  CONCLUSIONS
  The results of the current study confirm that BAX is an important target gene in ECs with MI. The frequent detection of IGFRII frameshift mutations in lymph node metastases suggest that IGFRII may play a role in tumor progression in these patients.
authors.affiliation: Department of Pathology, Hospital Santa Creu i Sant Pau, Autonomous University of Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Catasus
authors.forename: X
authors.initials: X
authors.lastname: Matias-Guiu
authors.forename: P
authors.initials: P
authors.lastname: Machin
authors.forename: G F
authors.initials: GF
authors.lastname: Zannoni
authors.forename: G
authors.initials: G
authors.lastname: Scambia
authors.forename: P
authors.initials: P
authors.lastname: Benedetti-Panici
authors.forename: J
authors.initials: J
authors.lastname: Prat
mesh_terms: D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein