Prognostic implications of BAX and TGFBRII mutations in colon cancers with microsatellite instability.
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.
Samowitz
Wade S
WS
Department of Pathology, University of Utah, Salt Lake City, Utah 84132, USA. wsamowitz@msscc.med.utah.edu
Curtin
Karen
K
Neuhausen
Susan
S
Schaffer
Donna
D
Slattery
Martha L
ML
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
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