title: Prognostic implications of BAX and TGFBRII mutations in colon cancers with microsatellite instability.
abstract: Microsatellite instability in sporadic colon cancer is associated with an improved prognosis. Recent studies, however, have suggested that microsatellite unstable cancers with mutations in the proapoptotic gene BAX have a relatively poor prognosis, whereas those with mutations in transforming growth factor-beta receptor type II (TGFBRII) have a relatively good prognosis. Using instability in the non-coding mononucleotide repeat BAT-26 as a measure of generalized microsatellite instability, we evaluated the prognosis of unstable colon cancers with and without frameshift mutations in the coding mononucleotide repeats of BAX and TGFBRII in a population-based sample of 1,427 individuals. BAX mutations were identified in 39.0% (64/164) of unstable colon cancers, whereas TGFBRII mutations were identified in 79.3% (138/174) of unstable colon cancers. Unstable colon cancers with and without instability in BAX and TGFBRII were associated with very similar and statistically indistinguishable percentage 5-year survivals and Kaplan-Meier survival curves; stable colon cancers were associated with a significantly worse 5-year survival and Kaplan-Meier survival (P < 0.001 and P < 0.013, respectively, compared against BAT-26 unstable). The age- and stage-adjusted risk of death associated with BAX or TGFBRII mutations was not significantly different from that of unstable tumors without such mutations. We conclude that instability-induced mutations in BAX or TGFBRII do not have a significant impact on the good prognosis of colon cancers with microsatellite instability.
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah 84132, USA. wsamowitz@msscc.med.utah.edu
authors.forename: Wade S
authors.initials: WS
authors.lastname: Samowitz
authors.forename: Karen
authors.initials: K
authors.lastname: Curtin
authors.forename: Susan
authors.initials: S
authors.lastname: Neuhausen
authors.forename: Donna
authors.initials: D
authors.lastname: Schaffer
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
mesh_terms: D003110:Colonic Neoplasms / Q000235:genetics*; D005500:Follow-Up Studies; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D015996:Survival Rate / Q000639:trends; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018125:Receptors, Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II