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Prognostic implications of BAX and TGFBRII mutations in colon cancers with microsatellite instability
Author(s) -
Samowitz Wade S.,
Curtin Karen,
Neuhausen Susan,
Schaffer Donna,
Slattery Martha L.
Publication year - 2002
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.10125
Subject(s) - microsatellite instability , colorectal cancer , frameshift mutation , population , medicine , cancer , biology , oncology , mutation , cancer research , gene , microsatellite , genetics , allele , environmental health
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‐β 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. © 2002 Wiley‐Liss, Inc.